The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 33 , Issue 2
Showing 1-30 articles out of 30 articles from the selected issue
  • Keigo NISHINO, Hideo OHKUBO, Mitsuo OHASHI, Saburo HARA, Junshi KITO, ...
    1983 Volume 33 Issue 2 Pages 267-278
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    The mode of action of a novel compound, 3-isobutyryl-2-isopropylpyrazolo [1, 5-a]pyridine (KC-404), as a potential anti-allergic agent has been investigated. KC-404 was shown to have a direct bronchodilator activity in guinea pig trachea in vitro and in anesthetized guinea pig in vivo. In addition, KC-404 had a fairly selective antagonistic action against slow reacting substance of anaphylaxis (SRS-A) on guinea pig ileum in vitro. In anesthetized guinea pigs, ED50 values for intravenously and intraduodenally injected KC-404 to inhibit SRS-A-induced bronchoconstriction were 0.0014 and 0.0065 mg/kg, respectively. Much higher doses were required to inhibit bronchospasms produced by histamine or particularly by acetylcholine. Orally administered KC-404, 0.001 to 0.1 mg/kg, also showed a selective inhibitory effect on increased vascular permeability by intradermal SRS-A in guinea pigs and rats. KC-404 inhibited the immunological release of mediators, notably SRS-A from sensitized guinea pig chopped lung in vitro at 10-8 to 10-4 g/ml. In vivo, the release of SRS-A, but not of histamine, mediated by a nonreaginic antibody in the peritoneal cavity of sensitized rats was inhibited by KC-404 at oral doses above 3 mg/kg. In a similar anaphylactic reaction but mediated by a reaginic antibody, KC-404 also inhibited SRS-A release at intraperitoneal doses of 2.5 to 10 mg/kg. The inhibitory activity on histamine release was less than half of that on SRS-A release. These results indicate that KC-404 is an orally active compound with a unique mode of action to inhibit preferentially both the effects and immunological release of SRS-A.
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  • Sadao NAKAYAMA, Mitsuaki SAKASHITA, Mayumi TONOOKA, Hiromi GOTOH, Haji ...
    1983 Volume 33 Issue 2 Pages 279-289
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Experimental hyperlipidemia and atherosclerosis induced by a cholesterol diet in SPF male and female rabbits (JW/KBL) were investigated by the determination of the lipid contents of the plasma, liver and thoracic aorta; determination of morphological changes of the aortic arch by head angiography; and computer tomography of the brain. Rabbits were fed the diet that contained 1% cholesterol for eight weeks. The plasma lipid levels began to rise from two weeks after the cholesterol dietwas started, reached the peak four to six weeks later, and then fell in both males and females at eight weeks. The cholesterol of the high density lipoprotein in male rabbit plasma was slightly increased by the cholesterol diet, but not in female rabbits. An increase in the total cholesterol (TC) and triglyceride contents of the liver and an increase in the TC and phospholipid contents of the thoracic aorta were observed at the eighth week. Histological examination of the aortic arch showed marked lipid vacuoles under the endothelial cells, noticeable lipid inclusions in the smooth muscle cells of the intima and granular prominences on the internal surface of the aorta. Head angiography of rabbits fed the cholesterol diet revealed a constriction of the lumina of several arteries due to the lipid depositions. These results suggest that hyperlipidemia and atherosclerosis can be produced at the eighth week using SPF rabbits fed on a cholesterol diet.
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  • Tomitaro KITA, Taeko HATA, Akio NAMIMATSU, Eiji ITOH
    1983 Volume 33 Issue 2 Pages 291-299
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    In order to clarify to a greater extent its action on peripheral nerves, various experiments were conducted using denervated animals to determine the effects of the nervous sedative, Neurotropin (NSP, containing many types of polysaccharides), on the site considered to be the periphery of autonomic nerves and the central nervous system. The increase in response to ACh due to bilateral cardiac vagotomy was significantly inhibited by a daily administration of NSP, but the increase in the response to noradrenaline (NA) due to celiac sympathectomy was hardly affected by this administration. The supersensitivity to the muscarinic action of ACh or methacholine of a denervated rat vas deferens, owing to ablation of the serous membrane, was significantly inhibited by the daily administrations of NSP. However, supersensitivity to NA was hardly affected. NSP never had any effect on the increase in the NA response of the duodenum and vas deferens isolated from mice given 6-hydroxydopamine, an adrenergic degenerator. Thus, an inhibitory action of NSP on denervation-supersensitivity is conceivably exerted on the parasympathetic nerves, rather than on the sympathetic nerves, and on a muscarinic receptor site, instead of a nicotinic site.
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  • Kenji YAMADA, Motohiro IIZUKA, Osasi TAKAITI
    1983 Volume 33 Issue 2 Pages 301-308
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    The effect of trimebutine maleate (TM-906) on bethanechol-induced contractions of the gastrointestinal tract in dogs was studied by means of chronically implanted force transducers, and it was compared with that of metoclopramide and atropine. During the period of motor quiescence in the fasted state of conscious dog, a bolus i.v. injection of 10 to 50 μg/kg bethanechol caused rhythmic contractions in the stomach and small intestine, in which an increase in basal tone was often accompanied in the distal ileum. The stomach responded to a less extent than the small intestine. Intravenous infusion of TM-906 at 3.0 mg/kg-hr for 20 to 60 min reduced the gastric contractions induced by 20 to 30 μg/kg bethanechol in five out of six conscious animals examined. The drug, however, enhanced the contractions of the duodenum and jejunum in a majority of the animals. Metoclopramide (1.8 mg/kg-hr) showed a tendency to potentiate the bethanechol-induced contractions in the stomach and small intestine, and atropine (0.06 mg/kg-hr) diminished them. In pentobarbital-Na anaesthetized dogs, effects of TM-906 on bethanechol-induced contractions resembled those in conscious dogs, inhibition in the stomach and potentiation in the small intestine.
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  • Isamu AKIBA, Hitoshi ENDOW, Tsutomu SUZUKI, Saizo YANAURA, Fuminori SA ...
    1983 Volume 33 Issue 2 Pages 309-317
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Attempts have been made to examine the relationship between urinary excretion of sex-dependent low molecular weight proteins found only in male rats (LMWP) and morphine physical dependence. Chronic administration of morphine produced a dose-related decrease in urinary LMWP excretion, which was correlated to the intensity of withdrawal signs including body weight loss and abnormal behaviors recognized after naloxone challenge. Furthermore, a statistically high correlation was obtained between the decrease in urinary LMWP excretion and the loss of body weight precipitated by naloxone challenge. LMWP was identified immunologically in the livers, kidneys, and sera using an antibody against purified LMWP. The serum level of LMWP was increased rapidly following bilateral nephrectomy. After chronic treatment with morphine, the LMWP content in the livers, kidneys, and sera were decreased. These findings indicate that the decrease in urinary LMWP excretion induced by chronic administration of morphine can be a useful parameter to assess the development of physical dependence on narcotics on the peripheral level without requiring drug withdrawal and naloxone challenge. This decrease in urinary LMWP may be caused by the inhibition of LMWP synthesis in the liver.
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  • Tsuneyuki YAMAMOTO, Naoe TAZOE, Showa UEKI, Kyoichi SHIMOMURA, Hisashi ...
    1983 Volume 33 Issue 2 Pages 319-325
    Published: 1983
    Released: November 07, 2006
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    The effect of zotepine, a new neuroleptic, on head-twitch induced by L-5-hydroxytryptophan (L-5HTP), mescaline and 2, 5-dimethoxy-4-methylamphetamine (DOM) in mice and rats was compared with that of known neuroleptics and the serotonin receptor blocker cyproheptadine. Among the neuroleptics tested, zotepine and haloperidol produced potent inhibitory effects on head-twitch induced by these three drugs. The results indicate that zotepine has a potent anti-hallucinogenic effect.
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  • Katsuo KOIKE, Issei TAKAYANAGI
    1983 Volume 33 Issue 2 Pages 327-333
    Published: 1983
    Released: November 07, 2006
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    Beta-adrenoceptor mechanisms were studied in the isolated guinea-pig taenia caecum. Isoprenaline, desisopropylprocaterol and carteolol relaxed guinea-pig taenia caecum, and their intrinsic activities (mean±S.E.) were 1.0, 0.95±0.03 and 0.61±0.08, respectively. The pD2 values (mean±S.E.) were 8.59±0.06 for isoprenaline, 7.94±0.21 for desisopropylprocaterol and 6.35±0.14 for carteolol. The β-adrenoceptors in guine-apig taenia caecum were irreversibly inactivated by photoaffinity labeling with isoprenaline (6×10-6 M). Photoinactivation of β-adrenoceptors caused a considerable parallel shift in the dose-response curve of isoprenaline. The decline of the dose-response curves of desisopropylprocaterol and carteolol without a preceding shift was observed after photoinactivation. Isoprenaline, desisopropylprocaterol and carteolol increased cyclic AMP levels in guinea-pig taenia caecum, and the pD2 values were 7.43, 6.97 and 5.96, respectively. When differences between the pD2 values for test drugs obtained from the mechanical responses and from the increases of cyclic AMP levels were calculated, the differences for isoprenaline was larger than those for desisopropylprocaterol and carteolol. The dose-response curves for relaxation and cyclic AMP level by isoprenaline were both shifted to the right as a result of prior incubation with carteolol. These results suggest that there are spare receptors for isoprenaline, but few for desisopropylprocaterol and carteolol in the smooth muscle.
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  • Carlo Alberto MAGGI, Guglielmo GRIMALDI, Alberto MELI
    1983 Volume 33 Issue 2 Pages 335-341
    Published: 1983
    Released: November 07, 2006
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    The effects of intravenous nifedipine and verapamil against the contraction produced by topical application of 54 mM K+ on the outer surface of rat duodenum, jejunum, ileum, caecum, colon and rectum have been investigated. Both drugs exhibited a descending gradient of relaxant activity with the exception of the rectum, verapamil being 1/3-1/4 as potent as nifedipine in all the test systems studied. Since these drugs at effective spasmolytic doses significantly affect heart rate and systemic blood pressure, their use as smooth muscle relaxants in intestinal disturbances would present several drawbacks
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  • Shigeru KIGOSHI, Matomo NISHIO, Mamoru KOKUBO
    1983 Volume 33 Issue 2 Pages 343-348
    Published: 1983
    Released: November 07, 2006
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    Dextromethorphan, dimemorfan, dihydrocodeine and oxymethebanol, centrally acting antitussives, were examined for their effect on Ehrlich carcinoma cells and sarcoma-180 cells in vitro or in vivo. The tumor cells were suspended in Hanks balanced salt solution (pH 7.4) supplemented with 2% bovine albumin, and they were incubated with and without 1 mM drugs at 37°C for 120 min. The incubation of the tumor cells with dextromethorphan or dimemorfan resulted in a decrease in the proportion of the viable cells (less than 25% after 120 min). However, no significant change was observed in the proportion of the viable tumor cells during the incubation with and without the other drugs (80-83% after 120 min). In addition, mice given the tumor cells i.p. were injected intraperitoneally with drugs (20-80 mg/kg/day) once daily for 5 successive days, and their survival time was observed. There was a slight difference in the survival time between mice treated with and without dextromethorphan or dimemorfan. However, a significant difference was found in the survival time between mice treated with and without dextromethorphan when mice given Ehrlich carcinoma cells were injected with the drug (40 mg/kg/time) twice a day for 5 days (about 18 days and 29 days). These results indicate that dextromethorphan and dimemorfan are cytotoxic to the tumor cells in vitro and in vivo.
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  • Hiroichi NAGAI, Tamotsu TAKIZAWA, Ichiro NAKATOMI, Naosuke MATSUURA, A ...
    1983 Volume 33 Issue 2 Pages 349-355
    Published: 1983
    Released: November 07, 2006
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    The effects of three glucocorticoids (steroids: hydrocortisone, prednisolone and dexamethasone) on IgE antibody-mediated immediate hypersensitivity reactions in rats were studied. Forty-eight hr homologous passive cutaneous anaphylaxis (PCA) was inhibited in a dose response manner by the administration of steroids 2 hr prior to challenge. When steroids were administered at various times before challenge, each steroid showed different patterns of time courses for inhibition of homologous PCA. Maximum inhibition was obtained 2 hr after the administration of each steroid. The IgE antibody-mediated histamine release from peritoneal mast cells in vivo was inhibited by the administration of steroids. Time-courses for the inhibitory effects of steroids on histamine release were slightly different from those in PCA. The increase of capillary permeability caused by histamine, serotonin, trypsin or hyaluronidase in the rat skin was not affected by steroids. The inhibitory action of steroids on PCA was not influenced by non-corticoidal steroids (17α-methyltestosterone, androstenedione and progesterone) or arachidonic acid. These results partially explain the inhibitory action of steroids on IgE antibody-mediated immediate hypersensitivity. The inhibition of histamine release would contribute towards the anti-allergic action of steroids but not the antagonistic effect on the mediators. Also the action of glucocorticoids receptor or the inhibition of arachidonic acid production are not vitally important in connection with the antiallergic action of steroids.
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  • Hiroyasu SATOH, Keitaro HASHIMOTO
    1983 Volume 33 Issue 2 Pages 357-362
    Published: 1983
    Released: November 07, 2006
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    Effects of ftorafur and 5-fluorouracil (5-FU) on the canine sinoatrial node were studied using isolated sinoatrial node and an atrial preparation which were obtained from puppies and perfused with oxygenated Tyrode solution through the dorsal right atrial artery (sinus node artery). The injection of ftorafur and 5-FU caused positive inotropic and chronotropic effects. However, the solvent of 5-FU caused similar effects. These positive inotropic and chronotropic effects were not abolished by pindolol. Verapamil did not alter the effects of ftorafur and 5-FU. Also a change in extracellular calcium concentration and aminophylline did not affect the positive chronotropic and inotropic responses to the two agents. These findings suggest that ftorafur may induce the positive responses by direct action.
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  • Hisashi SATOH, Yoshihiko SATOH, Jo MORI
    1983 Volume 33 Issue 2 Pages 363-372
    Published: 1983
    Released: November 07, 2006
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    The effect of zotepine (2-chloro-11-(2-dimethyl-aminoethoxy) dibenzo [b, f] thiepin), a new neuroleptic, and other neuroleptics, minor tranquilizers, antidepressants, anticholinergic drugs, antihistamine drugs, antiparkinsonian drugs, α-, β-adrenergic blocking agents, hypnotics and central muscle relaxants on apomorphine (APM)- and methamphetamine (MAP)-induced rotational behaviour was investigated in rats with unilateral lesions of the substantia nigra. Only the neuroleptics dose-dependently depressed both rotational behaviours. The minor tranquilizers also depressed both behaviours, but their effect was non-specific. The neuroleptics could be divided into two groups according to their relative effect on the APM- and MAP-induced rotational behaviour. The high-ratio group (fluphenazine, haloperidol, perphenazine, pimozide and zotepine) depressed the MAP-induced rotational behaviour more strongly than the APM-induced one, whereas the depressive effect of the low-ratio group (chlorpromazine, levomepromazine, thioridazine and clozapine) was the reverse. Zotepine, while belonging to the high-ratio group, was markedly lower in ratio than the other neuroleptics in this group. The correlation between the different effect of the two groups of neuroleptics and their clinical effect is discussed.
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  • Eiji MAKI, Michiko KONDO, Masayuki KEMI, Kenzaburo TANABE
    1983 Volume 33 Issue 2 Pages 373-383
    Published: 1983
    Released: November 07, 2006
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    Causal relationships of carbidopa and its related drugs on the development of spontaneous autoimmune hemolytic anemia (AIHA) in NZB mice were studied, and the following results were obtained: 1) Long term treatment with carbidopa (3 mg/kg/day) and levodopa (30 mg/kg/day) neither accelerated nor suppressed the development of spontaneous AIHA in NZB mice. 2) In mice treated with carbidopa/levodopa (3/30 mg/ kg/day), microhematocrit levels were lower than those in the control mice on and after 20 weeks of age and showed a significant decrease at 66 weeks of age (P<0.05). The average anti-RBC antibody titers reached the maximum level 8 weeks earlier than the control group. 3) Microhematocrit levels in the α-methyldopa (60 mg/kg/day)-treated group were higher than those in the control group, and at 66 weeks of age, they were decreased below that in the control group. The elevation of anti-RBC antibody titers was slower than that in the control group. As the reason for the weak effectiveness of α-methyldopa on the incidence of AIHA, it might be considered that the dosage employed was not sufficiently high enough and/or it may be due to the species difference between man and animals. Further studies are necessary in order to draw a conclusion on the AIHA-inducing ability of carbidopa.
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  • Kazuo MATSUI, Kenji HIGASHI, Kohji MIYAZAKI, Kohji FUKUNAGA, Masao MAE ...
    1983 Volume 33 Issue 2 Pages 385-393
    Published: 1983
    Released: November 07, 2006
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    We report on hormonal regulation of protein kinases in the rabbit myometrium. The injection of estrogen or progesterone produced 5.2±0.7 or 4.7±0.4-fold increases, respectively, of the total activity when histone was used as the substrate in the cytosol fraction of the tissue. The analysis of the activity by DEAE-cellulose column chromatography revealed that estrogen had no effect on increases in the levels in both types I and II cAMP-dependent protein kinases, on the basis of mg protein, while progesterone produced a 50% decrease in type I cAMP-dependent protein kinase and a 50% increase in type II cAMP-dependent protein kinase. Thus, the activity ratio of types II to type I did not change by treatment with estrogen and increased from 2.8 to 7.9 with progesterone administration. As the activity patterns by treatment with human chorionic gonadotropin closely resembled those seen with progesterone, our findings in case of the latter hormone are probably valid. The results indicate that the levels of protein kinases in the myometrium are altered in response to estrogen and progesterone and may possibly be involved in the physiological functions of the tissue.
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  • Saizo YANAURA, Katsuhiko KAKUNO, Kenzo NAKAO, Eijiro TAGASHIRA
    1983 Volume 33 Issue 2 Pages 395-402
    Published: 1983
    Released: November 07, 2006
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    A single injection of barbital increased glycogen, while it decreased glucose and glucose-6-phosphate levels in the rat brain. In long barbital dosing (36 days), however, the metabolite level of carbohydrate was almost recovered to the non-treated level. At the later stage of withdrawal (24-48 hr), all metabolites examined except lactate decreased. Only lactate increased remarkably. The effect of barbital dosing and withdrawal was almost same in the three portions, i.e., the cerebral cortex, brain stem, and cerebellum. Barbital depresses the central glycometabolism, and at the dependent stage (long term barbital dosing, 36 days or more), metabolism was almost same as the control. At the later period of withdrawal, it appeared that lactate was increased because of the hypoxic condition caused by stroke. In conclusion, carbohydrate metabolism can probably serve as a sensitive measure for the development of barbital dependence and the onset of withdrawal.
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  • Keishiro SHIMURA, Hitoshi ITO, Hiroshige HIBASAMI
    1983 Volume 33 Issue 2 Pages 403-408
    Published: 1983
    Released: November 07, 2006
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    On crossed immunoelectrophoresis, human serum C3 (the third component of complement) converted by antitumor polysaccharides (ATSO [antitumor polysaccharide oral], AB-P [Agaricaus blazei/polysaccharide], GU-P [Grifora umbellata polysaccharide], PS-K [polysaccharide Kureha] and zymosan) moved faster than native C3, appearing as the 3rd peak. The ratio of height of the 3rd peak to the α2-macroglobulin (α2-M) peak was linearly proportional to the dose of ATSO. At the dose of 500 μg/ml antitumor polysaccharides, the ratios were higher than 0.76, and the ratios for the serum treated with polysaccharide of no antitumor activity (dextran and gum arabic) were less than about 0.52. This ratio readily determined in vivo can be used as a measure for the antitumor activity of polysaccharides.
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  • Meng Kwoon SIM, Judy Meng Ee LIM
    1983 Volume 33 Issue 2 Pages 409-413
    Published: 1983
    Released: November 07, 2006
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    Methoxamine, isoprenaline, salbutamol and dobutamine were used to inhibit the spontaneous contraction of various rabbit small and large intestinal sections. From the concentration of the drugs that produced a similar magnitude of inhibition of the spontaneous contraction, the following deductions were made: The small intestine compared to the large intestine responded more to methoxamine, indicating a predominant presence of α receptors in the small intestine. The reverse is true for isoprenaline, indicating a predominant presence of β receptors in the large intestine. Salbutamol exerted a much greater effect on the large intestine than on the small intestine, indicating that the β receptors of the large intestine are mainly of the β2 type. The reverse is true for dobutamine, suggesting that the β receptors of the small intestine may be mainly of the β1 type. The second deduction agreed with the findings of Nakahata and co-workers who reported similar, though qualitative, findings in the rat and rabbit intestine. The third and fourth deductions are interesting in that the facts complement the century old acupuncture classification of paired meridian which grouped the lung and large intestine as a pair and the heart and small intestine as another pair. The lung has β2 and the heart β1 receptors.
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  • Eijiro TAGASHIRA, Tameo HIRAMORI, Tomoko URANO, Saizo YANAURA
    1983 Volume 33 Issue 2 Pages 415-422
    Published: 1983
    Released: November 07, 2006
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    The effects of cerebral monoamine-related substances during the course of formation of barbital (B) dependence were studied in male S.D. rats by the B-admixed food method. The monoamine-related substances, p-chlorophenylalanine (PCPA), tranylcypromine (Tcp), α-methyl-p-tyrosine (α-MT), methamphetamine (MA) and reserpine were administered during each B treatment period, except in the control group that was fed a food admixed with B only. All groups were examined for B withdrawal signs during each of 2 B withdrawal periods. Compared with the control group, B withdrawal signs tended to be mild in the PCPA-treated group, remained similar in the Tcp-treated group, were severe in the α-MT-treated group, very mild in the MA-treated group, and very severe in the reserpine-treated group. These findings suggested B withdrawal signs may tend to be reduced in severity if the activity of catecholaminergic neurons is kept elevated during the course of formation of physical dependence on B, and they suggested that acquirement of tolerance to and formation of dependence on barbiturates tend to be reduced under a condition of reduced cerebral 5-HT activity.
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  • Hitoshi ENDOU
    1983 Volume 33 Issue 2 Pages 423-432
    Published: 1983
    Released: November 07, 2006
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    Two components of the renal cytochrome P-450 (P-450) monooxygenase system, P-450 and NADPH-cytochrome c (cyt. c) reductase, were estimated using rabbit kidney slices and isolated nephron segments. Renal P-450 was distributed in the mitochondrial and microsomal fractions of both slices and nephron segments. P-450 (mitochondrial plus microsomal) was localized exclusively in the proximal tubule, with the highest activity in the S2 portion (18.14±5.47 fmoles/mm, 134.4 fmoles/μg protein). Intraperitoneal injection of 3, 4-benzo(a)pyrene (BP) induced a 2-fold increase of only the microsomal P-450. The intraproximal site of BP action was localized in a definite portion, a segment 3 to 6 mm distant from the glomerulus (49.0±7.7 to 103.9±3.5 fmoles/μg protein), suggesting that inducible P-450 molecules may be enriched in this portion. Multiplicity of renal P-450 could be demonstrated electrophoretically. Comparison of the pattern from BP treated rabbits with control hemeprotein indicated that BP induced a higher molecular weight P-450. The highest concentrations of NADPH-cyt. c reductase were distributed in the cortical microsomes, although it was also detectable in the papilla. The reductase was distributed along the entire single nephron, with highest concentrations in the S2 portion of the proximal tubule. In conclusion, the P-450 monooxygenase system is localized in the proximal tubule and in the control condition, the highest activity is found in the S2 portion.
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  • Takashi MATSUBARA, Satoru MORI, Akira TOUCHI, Yoko MASUDA, Yasuyoshi T ...
    1983 Volume 33 Issue 2 Pages 435-445
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    The hepatotoxic effect of carbon tetrachloride (CCl4), reflected by augmented blood aspartate aminotransferase and alanine aminotransferase activities and the extent of histological liver damage, was observed following oral administration of CCl4 to rats. A marked increase of blood transaminase activities and severe degeneration of hepatocytes in the centrilobular region were detected 1-2 days after the administration, while the cytochrome P-450 content and the drug metabolizing activity in livers were depressed immediately after the administration. Based on these results, the effect of CCl4 on hepatic cytochrome P-450 and the histological pattern of liver cells was observed using tissue samples obtained from various liver lobes of rats given CCl4 24 hr previously. Dose-dependent inactivation of cytochrome P-450 by the administration of CCl4 was observed throughout the liver, with the most extensive decrease in the cytochrome content in the median lobe. The extent of liver damage (hydropic swelling degeneration and central necrosis in lobule) was also greater in the median and right liver lobes than in the left lobe. When a small amount of CCl4 was administered, degeneration of liver cells was detected only in the median and right lobes with only slight degeneration in the left lobe. These results indicate different susceptibilities of rat liver lobes to CCl4.
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  • Hiroshi TANAKA, Katsuichi SHUTO, Nobuhiro NAKAMIZO
    1983 Volume 33 Issue 2 Pages 447-454
    Published: 1983
    Released: November 07, 2006
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    The influences of non-steroidal anti-inflammatory drugs (NSAID) on acetic acid ulcer were examined in rats. NSAID used in this study were aspirin (ASP, 200 mg/ kg), indomethacin (IND, 2 mg/kg) and phenylbutazone (PHE, 100 mg/kg). These NSAID were administered consecutively for 5 days once a day at the early stage of the ulcer. Eleven days after the ulceration, suppression of the healing was observed in rats treated with all of the NSAID. I n the rats treated with either AS P or I N D, a delay of healing was observed not only 11 days after ulceration, but also 16 days after ulceration. The ulcer index in rats treated with either ASP or IND 16 days after ulceration was greater than that at 11 days after ulceration. Further studies were performed regarding the progressive change of mucosal hexosamine content, gastric secretion and gastric emptying during the healing process of the ulcer. It was found that the increase of hexosamine plays an important role in the healing of the ulcer and that a durable fall in hexosamine content was related to the remarkable exacerbation of ulcer induced by either ASP or IND. Hypersecretion, back diffusion of hydrogen ion or a delay of gastric emptying cannot be regarded as a cause of the exacerbation of the ulcer.
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  • Hiroshi TAKEDA, Miwa MISAWA, Saizo YANAURA
    1983 Volume 33 Issue 2 Pages 455-461
    Published: 1983
    Released: November 07, 2006
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    The effect of bromhexine on behaviors of lysosomal enzymes in the submucosal gland was investigated using canine tracheal slice preparations, with reference to the histochemical chances in acid glycoproteins (AGP) in the gland. Incubation of tracheal slices with 1 % Triton X-100 or 0.0004-0.04% bromhexine for 30 min decreased the number of stained lysosomes in the glandular cells. The decrease in stained lysosomes after treatment with 1 % Triton X-100 or 0.04% bromhexine was effectively prevented by addition of 5% lecithin. The number of glandular cells that were stained red (stain index R) in the combined alcian blue at pH 2.5 and periodic acid-Schiff procedure markedly increased by treatment with 1 % Triton X-100 or 0.0004-0.04% bromhexine. In the bromhexine treated groups, there was a close correlation (r=0.932, P<0.01) between the increase in the number of glandular cells showing the stain index R and the decrease in the number of stained lysosomes in the cells. These findings suggest that the enzymes which are liberated from lysosomes into the cytoplasm by bromhexine may, at least in a part, be involved in the mucolytic action of the agent on AGP contained in mucus granules of the submucosal gland.
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  • Yukihiro OZAKI, Masatoshi HARADA
    1983 Volume 33 Issue 2 Pages 463-471
    Published: 1983
    Released: November 07, 2006
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    The ganglion blocking site of gardneramine (GA) and hirsutine (HS) was studied in the dog urinary bladder in an in situ preparation. GA and HS selectively inhibited the DMPP-induced contraction without having an antagonistic effect on the McN-A-343-induced and acetylcholine-induced contraction. In addition, since GA and HS showed a local anesthetic action weaker than that of procaine, the effect of procaine was studied on the same preparation. Procaine inhibited the McN-A-343-induced contraction, and it slightly inhibited the DMPP-induced and acetylcholine-induced contraction. From these findings, it is concluded that GA and HS inhibited the ganglionic transmission of the dog urinary bladder and that the blockade of the nicotinic receptor played a main role.
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  • L. H. Wang FU, Noboru TODA
    1983 Volume 33 Issue 2 Pages 473-480
    Published: 1983
    Released: November 07, 2006
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    In helically-cut strips of cerebral arteries isolated from dogs, serotonin, tryptamine, 5-hydroxytryptophan and tryptophan caused a dose-related contraction. The potency was in the order of serotonin>tryptamine>>5-hydroxytryptophan=tryptophan. In femoral arterial strips, only serotonin and tryptamine produced contractions. In cerebral arteries, the dose-response curve for serotonin was shifted to the right and downward by treatment with cinanserin, whereas in femoral and mesenteric arteries, the curves were shifted to the right. The contractile response of cerebral arteries to tryptamine was attenuated by cinanserin in concentrations above 10-7 M; however, 10-5 M was required to significantly reduce the response of femoral arteries. Phentolamine reduced the contractile response of femoral arteries to tryptamine, but not the response of cerebral arteries. It may be concluded that the different antagonism of cinanserin against the serotonin action on cerebral and femoral arteries is due to the ability of high concentrations of serotonin to induce relaxations of cerebral but not femoral arteries or to the different nature of receptors. Tryptamine appears to elicit contractions of cerebral arteries via a stimulation of tryptamine receptors, but elicit those of femoral arteries via stimulation of both alpha-adrenergic and tryptamine receptors. Whether or not receptors for serotonin and tryptamine are the same was riot determined.
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  • Takafumi NAGATOMO, Miyuki SASAKI
    1983 Volume 33 Issue 2 Pages 481-484
    Published: 1983
    Released: November 07, 2006
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  • Naoki O'HARA, Hiroshi ONO, Koroku HASHIMOTO
    1983 Volume 33 Issue 2 Pages 485-488
    Published: 1983
    Released: November 07, 2006
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  • Satoru SUNANO
    1983 Volume 33 Issue 2 Pages 489-491
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
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  • Akira KARASAWA, Ryoichi ISHITANI
    1983 Volume 33 Issue 2 Pages 492-494
    Published: 1983
    Released: November 07, 2006
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  • Shigetoshi CHIBA, Miyoharu KOBAYASHI, Masahiro SHIMOTORI
    1983 Volume 33 Issue 2 Pages 495-497
    Published: 1983
    Released: November 07, 2006
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  • Yutaka GOMITA, Yasuyuki ICHIMARU, Minehiro MORIYAMA
    1983 Volume 33 Issue 2 Pages 498-502
    Published: 1983
    Released: November 07, 2006
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