The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 31 , Issue 6
Showing 1-32 articles out of 32 articles from the selected issue
  • Hiroyuki KOHNO, Tsukasa SAKURADA, Tomoharu SUZUKI, Kensuke KISARA, Hir ...
    1981 Volume 31 Issue 6 Pages 863-873
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    We examined the changes in ingestive behavior, serum glucose (Glc) and free fatty acids (FFA) concentrations in male rats following intracerebroventricular (i.c.v.) injection of spermine (SPM). In satiated rats, over a 53.3 nmol of SPM suppressed feeding and drinking behavior in a dose-dependent manner. The median suppressive dose was 90.8 nmol for feeding behavior and 68.3 nmol for drinking behavior. Spermidine also suppressed ingestive behavior but the potency was appreciably weak compared to that of SPM, and the occurrence of the maximal suppression was observed 2-3 days later than that of SPM. The most significant anorexia and adipsia induced by SPM appeared between 16 and 36 hr after i.c.v. administration. SPM (180 nmol) produced a biphasic increase in serum Glc concentration. The 1st peak was at 1 hr and the other peak was 24 hr after the dosing. The same dose of SPM elevated serum FFA concentrations gradually, and the maximal increase appeared 24 hr after the injection. As less than a 120 nmol dose of SPM did not alter serum Glc and FFA concentrations, there seems to be no causal relation between SPM-induced anorexia, and changes in serum Glc and FFA concentrations. Nevertheless, the findings that a very small dose of SPM produced anorexia and adipsia support the possibility that SPM may play some functional role in the brain.
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  • Tadashi ISO, Hideyasu YAMAUCHI, Hiroshi SUDA, Katsuhiko NAKATA, Kazuo ...
    1981 Volume 31 Issue 6 Pages 875-882
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    (2R, 4R)-2-(2-Hydroxyphenyl)-3-(3-mercaptopropionyl)-4-thiazolidinecarboxylic acid (SA446) is a novel potent converting enzyme inhibitor having a sulfhydryl group in the molecule. SA446 inhibited the activity of semi-purified rabbit lung converting enzyme (1C50=6 nM). The contractile response of isolated guinea pig ileum to angiotensin I (Al) was markedly inhibited by SA446 (IC50=28 nM). On the other hand, SA446 augmented the contraction to bradykinin (BK) (AC50=0.7 nM), but did not affect the contraction caused by angiotensin II (AII), acetylcholine and histamine. These in vitro potencies of SA446 were 4 to 5 times larger than those of captopril. SA446 inhibited the pressor response to Al in rats (ID50=0.06 mg/kg, i.v., 0.48 mg/kg, p.o.) and dogs (ID50=0.01 mg/kg, i.v.). SA446 augmented the depressor response to BK (AD50=0.009 mg/ kg, i.v.), but did not affect the pressor responses to All and norepinephrine in rats. These in vivo activities of SA446 in dogs were more potent than those of captopril, but the reverse was seen in rats. Oral administration of SA446 had a hypotensive effect on two-kidney, one-clip renal hypertensive rats and spontaneously hypertensive rats, at doses over 3 and 10 mg/kg, respectively. However, the blood pressure of normotensive and DOCA-salt hypertensive rats was not affected by SA446, in doses up to 100 mg/kg. These results indicate that oral SA446 is a potent active inhibitor of converting enzyme and may be classed as an antihypertensive agent.
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  • Minoru ISHIZAWA, Shun'ichiro TANIGUCHI, Tsuneo BABA
    1981 Volume 31 Issue 6 Pages 883-889
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    The protective effect of sodium thiosulfate and thiourea on the lethal toxicity of the antitumor drug, cis-diamminedichloroplatinum (II) (cis-DDP), was investigated in bacteria and mice. Initially, the agents capable of antagonizing bactericidal activity of cis-DDP were screened using WP2 uvrA, a strain of E. coli sensitive to this drug. Of the ten sulfurcontaining compounds tested, thiourea and sodium thiosulfate exhibited potent protecting effects against cis-DDP cytotoxicity in bacteria. Propylthiouracil and methimazole showed intermediate levels of such protection, but the other 6 compounds had little or no protective effects. Thiourea and sodium thiosulfate were then subjected to the acute lethal toxicity test in mice to assess their protective activity in vivo. We found that cis-DDP i.v. lethality against mice can be blocked almost completely by excess amounts of thiourea or sodium thiosulfate. Thiourea protected against cis-DDP toxicity with a narrow range among the effective doses, while sodium thiosulfate was protective with a remarkably wide range of effective doses. The effectiveness of sodium thiosulfate was also indicated in experiments in which the LD50 dose of cis-DDP (16 mg/kg) i.p. increased over the level of>200 mg/kg with concomitant administration of sodium thiosulfate i.p.
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  • Masaki MAEDA-HAGIWARA, Kazuo WATANABE
    1981 Volume 31 Issue 6 Pages 891-896
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Induction of distinctive gastric antral ulcer by ergometrine in indomethacin-treated rats was investigated together with the gastric secretagogue property of this drug. Influence of several prophylactic drugs on indomethacin ulcer was examined, and among these drugs, ergometrine and methysergide were found to aggravate the gastric lesions. The aggravating effect was exerted exclusively in the pyloric antrum of rats and mice. Methysergide (20 mg/kg s.c.) and ergometrine (5-40 mg/kg s.c.), but not cyproheptadine (20 mg/kg s.c.), produced aggravation in pyloric antral lesions. This aggravating effect of ergometrine was also found in aspirin-induced gastric lesions in rats. However, in cold and restraint stress ulcers of rats, this effect was not apparent. Both ergometrine (0.5-2.5 mg/kg i.v.) and methysergide (2.5-5.0 mg/kg i.v.) stimulated gastric acid secretion, dose dependently, in anesthetized rats.
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  • Mohammed Rabiul ALAM
    1981 Volume 31 Issue 6 Pages 897-904
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Adult male mice were given 2.0 mg/kg of methampl etamine hydrochloride (MAM) for 6 times at 3-4 day intervals. The acute effects of MAM on locornotor activity of each mouse were investigated for 180 min after each administration. The motor-accelerating effect of MAM was progressively enhanced in parallel to the number of administrations. However, the enhancement of effect vvas not observed after repeated administration of MAM, when the mice were placed individually in narrow jars, which thereby perfectly inhibited ambulation during 180 min following each administration. The other mice were trained under the discriminated shuttle-type avoidance schedule (intertrial interval= 25 sec, CS presentation= 5 sec and 1 session= 1 hr). A slight influence of training on locomotor activity was detected after 2.0 mg/kg of MAM in the activity cage. A marked enhancement of the motor-accelerating effect was detected in the avoidance-trained mice, when 2.0 mg/kg of MAM was given for 5 times at 3-4 day intervals in the avoidance situation. These results suggest that the conditioned drug effect in association with environmental factors plays an important role in the production of enhancement.
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  • Kunio ISHII, Satoshi YAMAMOTO, Takamura MURAKI, Ryuichi KATO
    1981 Volume 31 Issue 6 Pages 905-909
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Effects of morphine on the force of contraction of rat vas deferens were investigated. Morphine and β-endorphin decreased the electrically evolved tvvitch tension, in a close dependent manner. The inhibitory effect of morphine, however, was much weaker than that of β-endorphin. These effects of both morphine and β-endorphin were completely antagonized by naloxone. In the presence of 30 μM morphine, the dose-response curve of β-endorphin shifted to the right by about 10-fold. Moreover, morphine partly reversed the contraction depressed by 0.3 μM β-endorphin, in a dose dependent manner. These findings suggest that morphine acts as a partial agonist on the rat vas deferens. Marked tolerance to β-endorphin and change in the antagonist potency of morphine were not observed in the vas deferens isolated from morphine-dependent rats.
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  • Yoshimi HACHINO, Takashi MATSUBARA, Bunji HAGIHARA
    1981 Volume 31 Issue 6 Pages 911-920
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Interaction of aminopyrine with microsomal membrane-bound cytochrome P-450 was studied spectrophotometrically at various pH. Aminopyrine-induced type I spectral change in untreated rat microsomes was observed in neutral and alkaline media, and the absorption magnitude between peak and trough in the spectra increased markedly by increasing pH. On the other hand, an anomalous spectral change (λmax, 425 nm; λmin, 410 nm) was obtained in acid medium, and the absorption magnitude of the anomalous spectral change was enhanced by decreasing pH. The spectral dissociation constant for the anomalous aminopyrine-binding reaction at pH 6.32 was about one order of magnitude greater than that for the type I binding reaction at pH 8.22. The type of aminopyrine-induced spectral change differed depending upon the age and pretreatment of animals. Neonatal microsomes elicited only the anomalous spectral change in all pH media. Liver microsomes from 3-methylcholanthrene-pretreated rats showed a reverse type I spectral change. Antipyrine produced only a reverse type I spectral change in all microsomes tested, and the absorption magnitude was enhanced by decreasing the pH. In the presence of a saturated concentration of a reverse type I compound, i.e., ethanol or antipyrine, aminopyrine induced the type I spectral change, even in acid medium. The binding mechanism of cytochrome P-450 with aminopyrine is discussed on the basis of these results.
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  • Yasuyuki SHIRAKI, Michitaka AKIMA, Hiroyuki NABATA, Yasuhiro OHBA, Eii ...
    1981 Volume 31 Issue 6 Pages 921-929
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    The hypotensive mechanisms of N-(2-hydroxyethyl) nicotinamide nitrate (SG-75, Nicorandil) were studied in anesthetized dogs. Intravenous injections of SG-75 (0.03-1 mg/kg) decreased systemic blood pressure (SBP) and increased peripheral (coronary, renal, mesenteric and femoral) blood flow (PBF) dose-dependently. The duration of the PBF increase, however, was much shorter than that of the SBP decrease. When peripheral vascular beds were perfused by means of a pump under a constant perfusion pressure near the SBP, the duration and magnitude of the SBP decrease and the PBF increase were equal. In doses of 0.03-0.3 mg/kg i.v., SG-75 did not significantly affect pulse pressure, heart rate, aortic blood flow, left ventricular pressure (LVP) and LVdP/dt max. Intra-arterial injections of SG-75 (0.003-1 mg) increased coronary, renal, mesenteric and femoral blood flow dose-dependently, without affecting SBP and cardiac function. In heart-lung preparations the drug (0.1-2 mg) did not cause cardiodepression. No hypotensive effect was observed following the administration of SG-75 (3 mg) into the cisterna magna. The results indicate that the hypotensive effect of SG-75 may be due mainly to its peripheral mechanisms, relating to vasodilation.
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  • Makoto MURAMATSU, Kinya KURIYAMA, Takehiko YUKI, Seitaro OHKUMA
    1981 Volume 31 Issue 6 Pages 931-940
    Published: 1981
    Released: November 07, 2006
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    Biochemical mechanisms underlying the development of alcoholic fatty liver were investigated. Acute ethanol (EtOH) administration for 3 days by an inhalation method, and continuous EtOH treatments by feeding with liquid diet or drinking water containing EtOH induced a significant increase of hepatic triglycerides (TG). A small but significant increase of TG was also observed in the blood serum. Although hepatic acetyl CoA carboxylase activity, measured in the presence and absence of citrate, was not altered by either acute or chronic EtOH administrations, fatty acid synthetase and malic enzyme activities in the liver were increased by continuous EtOH administration, but not in the acutely EtOH-treated animals. The incorporations of [14C]palmitate and [14C]acetate into hepatic RG were also increased significantly in animals treated continuously with EtOH. The lipoprotein lipase activity in adipose tissues was activated by both acute and continuous EtOH treatments, whereas lipase activity in adipose tissues and the epinephrine-stimulated and cyclic AMP-mediated release of free fatty acid (FFA) from this tissue were not altered by these treatments. These results indicate that acute alcoholic fatty liver is caused mostly by the increased mobilization of FFA from peripheral adipose tissues via the activation of lipoprotein lipase, whereas alcoholic fatty liver induced by continuous EtOH administration involves the increased synthesis of FFA due to the activation of fatty acid synthetase and malic enzyme in the liver in addition to the increased mobilization of peripheral FFA.
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  • Susumu OKABE, Haruyo KUNIMI
    1981 Volume 31 Issue 6 Pages 941-950
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Effects of a newly synthesized compound. N-acetyl-L-carnosine aluminum (CL-1700), on the formation of various types of acute gastric lesions were studied in rats. CL-1700 at 300 or 1, 000 mg/kg (p.o.) significantly inhibited Shay ulcers and water-immersion stress and aspirin-induced erosions in pylorus-ligated rats, and indomethacin- or phenylbutazone-induced erosions. CL-1700 had a weak effect on waterimmersion stress-induced erosions in rats with an intact pylorus. CL-1700 at 100 or 300 mg/kg (i.p.) significantly inhibited Shay ulcers and waterimmersion stress-induced erosions in rats with an intact pylorus. However, this compound (i.p.) had no effect on aspirin- and indomethacin-induced gastric erosions. CL-1700 at 1, 000 mg/kg (i.d.) significantly reduced the gastric acid output in pylorus-ligated rats but at 300 or 1, 000 mg/kg (p.o.) increased the volume, pepsin output and raised the pH value. The effects of CL-1700 on experimental gastric lesions were slightly weaker than those of aluminum sucrose sulfate but almost equal to or better than those of cimetidine. However, the effects of CL-1700 were much more potent than those of gefarnate. As CL-1700 appears to be a promising new anti-gastric lesion agent, the mechanisms of action are now under investigation.
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  • Saizo YANAURA, Naoto IMAMURA, Miwa MISAWA
    1981 Volume 31 Issue 6 Pages 951-956
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    We investigated the effect of β-adrenoceptor stimulants on the canine tracheal ciliated cells. A mucosal specimen of the tracheal membranous wall was placed in a chamber containing Hanks' solution. Membrane potential was recorded by an intracellular microelectrode, and ciliary beating was measured by a photoelectrical technique. lsoproterenol and salbutamol in 10-7 to 10-4 M caused a concentration-dependent increase in both frequencies of ciliary beating and small electrical oscillatories were superimposed on the membrane potential. Theophylline also increased frequencies of both activities in doses of 10-5 M and above. Onset of action of theophylline was later than that of isoproterenol or salbutamol. All the above drugs only slightly depolarized the membrane potential, in concentrations of 10-4 M. Propranolol (10-7-10-4 M) alone had little effect on ciliary beating and electrical activity. However, the effects of isoproterenol and salbutamol were effectively antagonized by propranolol (10-5 M). Dibutyryl cyclic AMP (10-7-10-4 M) caused concentrationdependent increases in ciliary beating and electrical activity. These results suggest that potent bronchodilators such as β-stimulants and theophylline increase the activity of tracheal ciliated cells by stimulating the intracellular cyclic AMP system.
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  • Saizo YANAURA, Naoto IMAMURA, Miwa MISAWA
    1981 Volume 31 Issue 6 Pages 957-965
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Many expectorants are clinically effective as they reduce viscosity and facilitate expectoration. There are, however, few reports on effects of expectorants on tracheal ciliated cells. We investigated the effects of N-acetylcysteine, ethylcysteine and bromhexine on the ciliary activities of the canine trachea. Ciliary movement was estimated using a phototransistor, and intracellular electrical activity was measured with a microelectrode method, in vitro. N-Acetylcysteine, ethylcysteine and bromhexine in low concentrations under a low perfusion rate (0.1 ml/min) produced an increase in the amplitude and frequency of ciliary beating, while N-acetylcysteine and ethylcysteine caused a cilio-depression in high concentrations. N-Acetylcysteine, ethylcysteine and bromhexine, under a low perfusion rate, did not affect the intracellular electrical activity. On the other hand, these three drugs under a high perfusion rate (1 ml/min) produced no change in the ciliary movement and the intracellular electrical activity in concentrations of 10-8-10-4 M. These results suggest that the increase in ciliary activity produced by the mucolytic drugs is not due to a direct effect on the ciliated cells, but rather to a mucolytic effect on the mucus around the cilia.
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  • Hitoshi KONTANI, Ryozo KOSHIURA
    1981 Volume 31 Issue 6 Pages 967-974
    Published: 1981
    Released: November 07, 2006
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    Afferent activities from receptors in the isolated lung of the bullfrog were recorded. Volley of afferent discharges synchronized with inflation of the lung and spontaneous discharges in the resting expiratory position were observed. When the solution of pH 9.5 was perfused in the pulmonary circulation, the rate of afferent discharges was slightly increased. When the pH was decreased to 5.5, the perfusion rate decreased and the rate of discharges was slightly increased initially, then markedly decreased. The amount of perfusion solution from the pulmonary vein per min and the firing frequency were almost restored to pretreatment level after the lung was perfused with normal Ringer's solution. When the temperature of the solution was from 20°C to 10°C, the rate of discharges was decreased. Epinephrine (1×10-4 M) and 4-aminopyridine (1×10-4 M and 1×10-3 M) produced an increase in the rate of discharges in proportion to decrease in the perfusion rate. Histamine (1×10-4 M) did not influence the firing frequency and the amount of perfusion solution from the vein per min. This method enables recording of the effect of drugs on the pulmonary afferent activities.
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  • Takao KOMABAYASHI, Seiya SAKAMOTO, Minoru TSUBOI
    1981 Volume 31 Issue 6 Pages 975-978
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    The aim of the present work was to study the mechanism of the mobilization of plasma lipids produced by histamine in the dog, in vivo. The increase of plasma lipids by histamine in vivo was suppressed by cimetidine, but not by diphenhydramine. Although, histamine increased the level of plasma adrenaline, adrenaline does not appear to contribute to the lipolysis stimulated by histamine, because propranolol and alprenolol, β-adrenergic blocking agents, did not affect the lipolysis stimulated by histamine. From these data it is concluded that the increase of plasma lipids in vivo is not attributable to the release of adrenaline from adrenal glands by histamine, but is produced by the stimulation through H2-receptors in fat cells.
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  • Hideaki KARAKI, Tadahiko SUZUKI, Norimoto URAKAWA
    1981 Volume 31 Issue 6 Pages 979-983
    Published: 1981
    Released: November 07, 2006
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    Effects of substitution for NaHCO3 (and 5% CO2) in the physiological solution with equimolar N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) or morpholinopropane sulfonic acid (MOPS) (and 100% O2) at various pH levels on the contractility of smooth muscle were examined. At pH 7.4, spontaneous contraction in rat portal vein was not inhibited by the artificial buffer solutions, as compared to findings in the case of bicarbonate buffer solution. Norepinephrine-dose response curve in the case of rat portal vein and the histamine-dose response curve in cases of guinea pig taenia coli remained unchanged in the artificial buffer solutions. At pH 7.2 and 7.0, the spontaneous contraction in portal vein was reversibly inhibited either in artificial or in bicarbonate buffer solutions. The norepinephrine and histamine-dose response curves shifted downwards and/or to the right in these low pH solutions. Thus, HEPES and MOPS had no inhibitory effect on the smooth muscle contractility. Since low pH strongly inhibited the contractility, attention should be directed to the temperature-dependent decreases in pKa of the artificial buffers (i.e., if pH of the solution is adjusted at room temperature and then warmed, pH decreases).
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  • Reiko HOBARA, Hajime YASUHARA
    1981 Volume 31 Issue 6 Pages 985-993
    Published: 1981
    Released: November 07, 2006
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    A thiamine (T) deficient state in rats was produced by feeding the rats a T deficient diet (TDD). At the stage of 13 days (TDD1 3 group), the number of red blood cells (RBC) and white blood cells (WBC), hematocrit (Ht) and hemoglobin (Hb) values decreased. On the other hand, after 30 days on the TDD (TDD30 group), the number of RBC was 819×104/ mm3 as against 631×104/mm3 in the normal control group (NC group). Ht and Hb values also increased in the TDD30 group. These changes observed in the TDD30 group were significantly different from findings in the equal weight control group (EWC group) or in the pair fed control group (PFC group). The number of reticulocytes increased, the levels of 2, 3-diphosphoglycerate (2, 3-DPG) of RBC decreased and plasma erythropoietin levels increased in the TDD30 group. T levels of blood in the TDD13 group were 62 (39-79) ng/ml as against 275 (196-412) ng/ml in the NC group. T levels of blood in the TDD30 group were 102(17-365) ng/ml, and widely varied. Decrease in 2, 3-DPG produces an increase in O2 affinity to Hb, and hypoxia is induced in the peripheral tissues. Furthermore these conditions stimulate erythropoietin production and finally the number of RBC increases. T deficiency produces anemia at an early stage and absolute erythrocytosis occurs at the late stage of T deficiency. The increased osmotic resistance of RBC in hypotonic solution was also observed in the TDD30 group. This increase in osmotic resistance correlated with the decrease in cholesterol and phospholipid levels in the membrane of RBC.
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  • Fukio KONNO, Issei TAKAYANAGI
    1981 Volume 31 Issue 6 Pages 995-1003
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Effects of 1, 1-diphenyl-3-piperidinobutanol hydrochloride (Aspaminol), a nonspecific smooth muscle relaxant, on the uptake of calcium in the synaptosomes of rat brain were studied, using two stimuli i.e. high KCl and ATP. We also studied the effect of Aspaminol on the analgesic response of rat hindpaw using the Randall-Sellito test. The addition of Aspaminol inhibited the stimuli-induced calcium uptake in a concentration dependent manner. Aspaminol inhibited the high KCl induced calcium uptake competitively against the external calcium concentration. These findings suggest that Aspaminol may act on the surface of the synaptosomal membranes. In case of ATP stimulated calcium uptake, Aspaminol reduced the rate of uptake and maximal level of the synaptosomal calcium, and did not appear to have any effect on the rate of calcium release. These findings suggest that the inhibitory effect of Aspaminol can be mainly attributed to inhibition of the calcium influx, but not to acceleration of calcium efflux. In the five weeks old rats, Aspaminol did not influence the responses in the paw pinch test, but, in the weanling rats (about three weeks old), Aspaminol had a slight effect on the responses in the paw pinch test. This discrepancy may be due to difficulties in passing through the blood-brain barrier. Our findings suggest that a certain relationship may exist between the analgesic effect and the calcium uptake in the synaptosomes.
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  • Yasumichi HAGINO, Masakatsu TACHIBANA
    1981 Volume 31 Issue 6 Pages 1005-1012
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Properties of cyclic AMP-dependent protein kinases from skeletal, heart and diaphragm muscles of hypothyroid rats were compared. Increased enzyme activity was observed in skeletal muscle from hypothyroid rats after DEAE-cellulose chromatography. Changes in isozyme distribution were also shown in the hypothyroid status. The elution profile on DEAE-cellulose suggested a possible translocation of the enzyme from the particulate to the soluble fraction in the heart of hypothyroid rats. The turnover rate of the enzyme protein decreased in the skeletal muscle of hypothyroid rats, but the other two organs showed no change even in the hypothyroid status. The activity of heat-stable protein kinase inhibitor increased in the skeletal and the diaphragm muscles in hypothyroid rats, whereas the activity in the heart decreased in the hypothyroid status. These data suggested the possibility that changes in enzyme properties, modification of isozyme distribution, and changes in modulator activity might account for the modulation of muscle function in hypothyroid rats.
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  • Yohko FUJIMOTO, Fujiko YASUOKA, Tadashi FUJITA
    1981 Volume 31 Issue 6 Pages 1013-1019
    Published: 1981
    Released: November 07, 2006
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    The effect of ascorbic acid and Fe2+ on p-aminohippurate accumulation by rat kidney slices was examined. Ascorbic acid and Fe2+ promoted lipid peroxidation of rat renal cortical slices was found to be dose related. Moreover, ascorbic acid (1.0 mM) and Fe2+ (0.4 mM) increased tissue water and decreased the accumulation of p-aminohippurate. The addition of N, N'-diphenyl-p-phenylenediamine (antioxidant) at the concentration of 1×10-6 M recovered the accumulation of p-aminohippurate by about 43%. The apparent Km of p-aminohippurate uptake was increased by ascorbic acid and Fe2+ with no change in the apparent V. These data suggest that ascorbic acid and Fe2+ can cause a significant alteration in p-aminohippurate and water transport of renal cortical slices and that these effects may be, at least, partly due to the lipid peroxidative action of ascorbic acid and Fe2+.
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  • Hideyo OHSHIKA, Haruo TAKEMURA, Junichiro ENDO, Shinichi HATTA, Mamoru ...
    1981 Volume 31 Issue 6 Pages 1021-1027
    Published: 1981
    Released: November 07, 2006
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    Isoproterenol (ISO)-induced amylase release from rat parotid slices was increased by the addition of methoxamine to either a normal or a calcium (Ca)-free medium. The potentiating effect of methoxamine was completely blocked by the addition of phentolamine, irrespective of whether the slices were incubated in the normal or the Ca-free medium; and the effect also disappeared after prolonged preincubation (60 min) of the slices in the Ca-free medium. Both verapamil and procaine reduced methoxamine-induced amylase release, but only verapamil blocked the stimulating effect of methoxamine in the normal medium. ISO-induced accumulation of cyclic AMP in the slices was unaffected by methoxamine or phenylephrine. The results suggest a possibility that the potentiating effect of methoxamine on ISO-induced amylase release may be independent of the presence of extracellular Ca and the increased accumulation of cyclic AMP in the tissue is unnecessary.
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  • Yoshihiko SAKAKIBARA, Ikunobu MURAMATSU, Motohatsu FUJIWARA, Yasunori ...
    1981 Volume 31 Issue 6 Pages 1029-1036
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Effects of guanabenz, a hypotensive agent, on the adrenergic mechanism were studied in isolated rabbit thoracic aorta and pulmonary artery and findings were compared with data obtained with clonidine and guanethidine. Guanabenz in concentrations higher than 10-6 M produced weak contractions which were attenuated by phentolamine or yohimbine. Such concentrations of guanabenz competitively inhibited the contractile response to noradrenaline, but did not attenuate the response to tyramine. In concentrations ranging from 10-8 to 10-7 M, guanabenz attenuated the contraction and the increase of 3H-efflux in response to transmural electrical stimulation of the pulmonary artery preincubated with 3H-noradrenaline. Phentolamine or yohimbine effectively blocked these inhibitory effects of guanabenz. Such effects of guanabenz were similar to those of clonidine and dissimilar to those of guanethidine. These results indicate that guanabenz acts on presynaptic and postsynaptic alpha receptors of the peripheral blood vessels, as in the case of clonidine and that the potency was almost the same as clonidine.
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  • Sakae FUJIMOTO, Masashi SASA, Shuji TAKAORI
    1981 Volume 31 Issue 6 Pages 1037-1042
    Published: 1981
    Released: November 07, 2006
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    Studies were performed to elucidate the role of dopamine originating in the pars compacta of the substantia nigra (SN) on caudate nucleus (CN) neurons receiving input from the motor cortex using cats anesthetized with α-chloralose. Activation with cortical stimulation was observed in 50 CN neurons, five out of which were also excited by SN stimulation. Conditioning stimuli applied to the SN, 30 msec preceding the test stimulus to the cortex, produced a significant inhibition of spike generation upon cortical stimulation in 28 out of 45 neurons tested and did not affect the remaining 17 neurons. The mean spike number of the 45 neurons was significantly reduced with SN conditioning stimulation. When dopamine up to 200 nA was iontophoretically applied to CN neurons, there was a significant inhibition of the spike generation with cortical stimulation in 9 out of 16 neurons. The mean spike number of the 16 neurons upon cortical stimulation was significantly reduced during dopamine application. In addition, a close correlation was observed between the effects of SN conditioning stimulation and iontophoretic dopamine. These results suggest that dopamine derived from the SN produces an inhibition of CN neurons receiving input from the motor cortex.
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  • Mariko OISHI, Chiyoko INAGAKI, Motokazu FUJIWARA, Shuji TAKAORI, Harua ...
    1981 Volume 31 Issue 6 Pages 1043-1049
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Neurotensin administered intravenously in a dose of 1 nmole/kg produced triphasic blood pressure responses in anesthetized rats: the first depressor, second pressor and third depressor responses. The first depressor response was significantly suppressed by treatment of animals with a mixture of diphenhydramine and metiamide or chronic administration of compound 48/80, but was not modified by treatment with atropine, phentolamine, yohimbine, propranolol, sulpiride and adrenalectomy. The second pressor response was abolished by phentolamine, yohimbine and adrenalectomy. The second phase response was also markedly reduced by diphenhydramine in reserpinized rats and chronic administration of compound 48/80. The third depressor response was blocked by treatment of animals with diphenhydramine or chronic administration of compound 48/80. These results suggest that neurotensin may produce an immediate depressor response (the first phase) partly through a histamine-mediated process, and the second pressor response is produced by catecholamines released from the adrenal medulla through a histamine-mediated process. The third depressor response appears to be mediated mainly by histamine. The participation of mast cells as an origin of histamine which mediates these processes is suggested.
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  • Shinobu IKUSHIMA, Ikunobu MURAMATSU, Motohatsu FUJIWARA, Katsuro ASHID ...
    1981 Volume 31 Issue 6 Pages 1051-1060
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Effects of Goniopora toxin (GPT) on cardiac action potential and on contractile force were investigated in isolated guinea-pig papillary muscle. GPT produced a positive inotropic effect by increasing contractile force and prolonging the relaxation time. The time-to-peak force was little affected. GPT prolonged the action potential duration but did not affect the resting membrane potential nor the amplitude of the action potential. Thus there was a correlation between the positive inotropic effect and prolongation of the action potential duration. Tetrodotoxin or a reduction in extracellular sodium concentration attenuated both the positive inotropic effect and the prolonged duration of the action potential induced by GPT. Lanthanum or a reduction in extracellular calcium concentration also inhibited the increased contraction but did not shorten the prolonged durations of contraction and action potential. Verapamil attenuated the positive inotropic effect by reducing both the contractile force and the duration of contraction, but did not shorten the action potential duration. These results show that the positive inotropic effect of GPT depends on the increase in both sodium and calcium influxes while the prolonging effect on the action potential probably depends only on an increase in sodium influx. Hence, it is concluded that the prolongation of the action potential due to the increased sodium permeability is an essential process for the appearance of the positive inotropic effect of GPT.
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  • Seitaro OHKUMA, Jun-ichi TAMURA, Kinya KURIYAMA, Tatsuro TAKINO
    1981 Volume 31 Issue 6 Pages 1061-1070
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Characteristics of taurine (2-aminoethanesulfonic acid) transport were studied in freshly isolated rat hepatocytes prepared by a collagenase perfusion technique. The uptake of taurine at 37°C was linear up to 30 min of incubation, but gradually decreased thereafter and reached a plateau at 90 min after initiation of the incubation. Taurine uptake at 4°C by isolated hepatocytes was not saturable, whereas that at 37°C was saturable with the following parameters: Km, 37 μM; Vmax, 0.043 nmoles/mg prot./min; and EA, 5.6 Kcal/mol. The taurine uptake at 37°C was found to be sodium dependent, and this was inhibited competitively by guanidinoethyl sulfonate and β-alanine with the Ki values of 1.75 mM and 285 μM, respectively. Conjugated cholate, conjugated chenodeoxycholate, alanine, isethionate and leucine had no effect on the taurine uptake. The present results indicate that taurine uptake by isolated hepatocytes consists of unsaturable and energy independent, and carrier-mediated and energy dependent transport processes.
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  • Naoko UEDA, Ikunobu MURAMATSU, Yoshihiko SAKAKIBARA, Motohatsu FUJIWAR ...
    1981 Volume 31 Issue 6 Pages 1071-1079
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    In the rabbit iris sphincter muscle, electrical transmural stimulation produced fast and slow components of contraction which were markedly attenuated by tetrodotoxin. The fast component was augmented by physostigmine and was abolished by atropine, while the slow component was little affected. Adrenergic and ganglionic blocking agents did not inhibit the slow component. Therefore, the fast component is probably cholinergic, while the slow one is noncholinergic, nonadrenergic in nature. Capsaicin did produce a considerable contractile response, but there was a gradual decline with repetitive application and a tachyphylaxis occurred. Under such conditions the slow but not the fast component was abolished. Substance P and acetylcholine produced the largest contraction, while ATP, histamine, serotonin and noradrenaline produced little or no response. In cold stored preparations, the responses to electrical transmural stimulation and capsaicin were either markedly attenuated or abolished, whereas substance P and acetylcholine produced considerable contractions. Baclofen and theophylline did not inhibit the slow response to electrical transmural stimulation or the response to substance P and capsaicin. Thus, electrical transmural stimulation produces cholinergic and noncholinergic, nonadrenergic contractions in the rabbit iris sphincter muscle and the latter response is considered to be mediated by substance P or a related peptide released from the neural components.
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  • Toshio NAKAKI, Takamura MURAKI, Yukiko TOKUNAGA, Ryuichi KATO
    1981 Volume 31 Issue 6 Pages 1081-1083
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
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  • Kooichi SAIDA, Akitoshi SUZUKI
    1981 Volume 31 Issue 6 Pages 1084-1086
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
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  • Takao KUBO, Masako YAMASHITA, Yoshimi MISU
    1981 Volume 31 Issue 6 Pages 1087-1090
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
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  • Yoshio GOSHIMA, Masayoshi KAIHO, Yoshimi MISU
    1981 Volume 31 Issue 6 Pages 1091-1094
    Published: 1981
    Released: November 07, 2006
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  • Masahiko MARUYAMA, Keisuke SATOH, Norio TAIRA
    1981 Volume 31 Issue 6 Pages 1095-1097
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
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  • Reiko HOBARA, Keiko OZAWA, Masako OKAZAKI, Hajime YASUHARA
    1981 Volume 31 Issue 6 Pages 1098-1100
    Published: 1981
    Released: November 07, 2006
    JOURNALS FREE ACCESS
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