The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
33 巻, 5 号
選択された号の論文の28件中1~28を表示しています
  • Shigehiko NARUMI, Yasuo NAGAI, Yoshiaki SAJI, Yuji NAGAWA
    1983 年 33 巻 5 号 p. 915-926
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    The effects of thyrotropin-releasing hormone (TRH) and its analog γ-butyrolactone-γ-carbonyl-L-histidyl-L-prolinamide citrate(DN-1417) on adenosine 3', 5'-monophosphate (cyclic AMP) and guanosine 3', 5'-monophosphate (cyclic GMP) levels in rat brain were investigated using a radioimmunoassay method. The time course of elevation of these nucleotides in various brain regions after administration of DN-1417 showed a peak at 5 to 15 min followed by a gradual decrease. DN-1417 (1 to 10 mg/ kg i.p.) caused a dose-related increase in cyclic AMP levels in the cerebellum, cerebral cortex, striatum, nucleus accumbens, thalamus, hypothalamus and brain stem; whereas significant increases in cyclic GMP were observed in the cerebellum, nucleus accumbens and brain stem. TRH (3 to 10 mg/kg i.p.) caused significant increases of cyclic AMP in the cerebellum, cerebral cortex, nucleus accumbens, thalamus and brain stem and also caused an increase in cerebellar cyclic GMP. With one exception, DN-1417, apomorphine (Apo), methamphetamine (MAP) (all, 3 mg/kg i.p.) and TRH (10 mg/kg i.p.)-induced increases in cyclic nucleotides were blocked by pimozide (1 mg/kg i.p., 4 hr before), a dopamine receptor blocker; the exception was a TRH-induced increase in cerebellar cyclic GMP. These increases were not blocked by propranolol (10 mg/kg i.p., 30 min before), an adrenergic β-receptor blocker. α-Methyl-p-tyrosine (α-MT, 250 mg/kg i.p., 4 hr before), a tyrosine hydroxylase inhibitor, almost completely blocked DN-1417- and MAP-induced increases in cyclic nucleotides, slightly blocked TRH-effects, and had no effect on Apo-effects. These in vivo results were confirmed in an in vitro system using brain slices. The addition of DN-1417 (10-4 M) or TRH (10-3 M) significantly enhanced the spontaneous [3H]-dopamine and [3H]-norepinephrine release from the superfused slices of the rat nucleus accumbens and cerebral cortex in vitro. The addition of DN-1417 (10-4 M) or TRH (10-4M) had no effect on the activities of adenylate cyclase and guanylate cyclase, although only a high concentration (10-3 M) of DN-1417 inhibited the cyclic AMP- and cyclic GMP-hydrolytic activities in various brain region homogenates. These results suggest that DN-1417 does not produce an increase in the levels of cyclic nucleotides by direct receptor-enzyme activation, but that DN-1417 like MAP causes the increase through endogenous catecholaminergic, particularly dopaminergic activation.
  • Hisashi KURIBARA, Sakutaro TADOKORO
    1983 年 33 巻 5 号 p. 927-931
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    Circadian variation in susceptibility to the ambulation-increasing effect of scopolamine in mice was investigated. The mice housed under a 12-hr light-dark situation (light period: 6:00-18:00 and dark period: 18:00-6:00) for 5 weeks were administered scopolamine HBr at 0.5 or 2 mg/kg s.c. at one of six times of the day (3:00, 7:00, 11:00, 15:00, 19:00 and 23:00), and the ambulatory activity was measured for 2 hr. Scopolamine induced a dose-dependent increase in the ambulatory activity. In addition, there was a clear circadian variation in the susceptibility to the ambulation-increasing effect of scopolamine. The highest and the lowest overall activity counts during the 2 hr observation period were found when the drug was administered at 3:00 and 15:00, respectively. The present results suggest that the susceptibility to scopolamine in mice is dependent on the time-of-day at which the drug is administered. The reasons which may induce this circadian variation in susceptibility to scopolamine are discussed.
  • Foo-Wah FOONG, Masamichi SATOH
    1983 年 33 巻 5 号 p. 933-938
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    Aversive (nociceptive) biting-like responses induced by micro-application of bradykinin solution onto rat tooth pulp were dose-dependently suppressed by nonnarcotic drugs such as baclofen and lidocaine as well as carbamazepine and phenytoin, which are employed for clinical treatment of trigeminal neuralgia. The potency order of these drugs on a molar basis is baclofen (4.20)>carbamazepine (1.00)>lidocaine (0.94)>phenytoin (0.19). Such responses were also inhibited by morphine, pentazocine and cyclazocine (potency ratio of the three general analgesics, 1.00:0.46:8.11 ), indomethacin (a non-narcotic and anti-inflammatory analgesic) and α-chloralose (an anesthetic). The latter drug produced an analgesic effect at doses much lower than those used for anesthesia. These findings suggest that our method is feasible for evaluating the activities of general and particular analgesic drugs in the trigeminal regions.
  • Takuji MIZUI, Masami DOTEUCHI
    1983 年 33 巻 5 号 p. 939-945
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    The participation of polyamines and nonprotein sulfhydryls in the gastric cytoprotective mechanisms was studied using gastric mucosal lesions produced by acidified ethanol in rats as an experimental model. Treatment with prostaglandin E2 (PGE2), but not cimetidine, prevented the formation of gastric mucosal lesions. Oral administration of cadaverine, spermidine and spermine prevented the lesion formation by acidified ethanol in a dose-dependent manner. Indomethacin or acetazolamide had no influence on the cytoprotective effect of spermine, whereas sulfhydryl blockers such as iodoacetamide and N-ethylmaleimide partially blocked it. Sulfhydryl compounds such as cysteine, reduced glutathione (GSH), and cysteamine prevented the lesion formation induced by acidified ethanol. The concentration of nonprotein sulfhydryls in the gastric mucosa was significantly decreased at 1 hr after administration of acidified ethanol, and this decrease was partially prevented by spermine or PGE2. These results suggest that the cytoprotective effect of spermine may not be mediated by endogenous prostaglandins or alkaline secretion in the gastric mucosa, but may be partially related to endogenous sulfhydryl compounds.
  • Yukio YONETANI, Kazumi IWAKI
    1983 年 33 巻 5 号 p. 947-954
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    A practical procedure for evaluating uricosuric agents was demonstrated using clearance experiments with potassium oxonate-treated rats. The fractional excretion value of uric acid showed a reabsorptive net flux of uric acid in the renal tubules of the animal, though the value was obviously higher than those of primates such as men, chimpanzees and cebus monkeys. However, the rats responded well to uricosuric drugs and diuretics. Probenecid and uricosuric diuretics such as tienilic acid induced hyperuricosuria due to the increase of fractional excretion of uric acid and/or the increase of the filtered amount of uric acid with the rise of plasma uric acid. On the other hand, furosemide had no effect on uric acid excretion at a low dose with moderate diuresis, while a higher dose decreased the fractional excretion of uric acid with elevation of plasma uric acid. Benzothiazides were also uricosuric at the lower doses, but the high dose, as in the case of the so-called uricosuric drugs, had no effect on the uric acid excretion and plasma uric acid level. Thus, oxonate-treated rats were useful for evaluating drug effects on uric acid excretion.
  • Makoto MURAMATSU, Makoto TANAKA, Susumu OTOMO, Hironaka AIHARA
    1983 年 33 巻 5 号 p. 955-963
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    Hydrocortisone (HC) in rat liver cytoplasmic fraction was bound to three different binding sites with high, medium and low affinity. Dissociation constants (Kd) were approx. 2.1, 22 and 208 nM; and the densities of these binding sites were about 40, 50 and 10% of total number of binding sites, respectively. The binding site for dexamethasone (DM) of the cytoplasmic fraction was the medium affinity one among these three components. The maximum number of binding sites (Bmax) of HC and DM was significantly increased by adrenalectomy. The Bmax of HC was about twice as great as that of DM in normal and adrenalectomized rat liver. DM inhibited 3H-HC binding in a dose-dependent manner but inhibition did not exceed 50% in either normal or adrenalectomized rats. Following adrenalectomy, the Bmax of the medium affinity-site for HC was significantly increased, while the high affinity component disappeared. By adding DM to the cytoplasmic fraction of adrenalectomized rat liver in vitro and in vivo, the Bmax of the medium affinity-site was significantly decreased, and a high affinity component of HC was revealed with a significant increase in the number of binding sites. These results indicate that the binding site for DM is one component of the HC binding site; and following adrenalectomy, the number of each type of binding site for glucocorticoids increases differently from the others.
  • Buichi FUJITANI, Junko MAEDA, Toshimichi TSUBOI, Toshiaki KADOKAWA, Ma ...
    1983 年 33 巻 5 号 p. 965-970
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    The effect of gliclazide, a hypoglycemic sulfonylurea, on the formation of prostaglandin (PG) I2 by the aortic rings of normal and streptozotocin-induced diabetic animals was studied. In in vitro experiments, gliclazide (100-300 μg/ml) enhanced the spontaneous PGI2 formation by the guinea-pig and rat aorta. Gliclazide also enhanced the transformation of both arachidonic acid and PGH2 to PGI2 in guinea-pig aorta, indicating that one of the main enhancing sites is the step of converting PGH2 to PGI2. In ex vivo experiments, the formation of PGI2 in the aorta of streptozotocin-diabetic rats was markedly reduced as compared with that of normal rats. An oral administration of gliclazide (100-300 mg/kg) significantly restored this reduced formation of PGI2 without any effect on blood glucose level. This enhancing effect of gliclazide may be favorable to the treatment of diabetic microangiopathy.
  • Saizo YANAURA, Hiroyuki MIZUNO, Kazuhiro GOTO, Junzo KAMEI, Tomokazu H ...
    1983 年 33 巻 5 号 p. 971-982
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    The effects of Ba598Br, a new atropine derivative possessing a quarternary ammonium salt structure, on the canine airway, including its antiasthmatic effects, were investigated. The in vivo airway resistance was determined using the modified Konzett-Rossler method. Inhalation of 0.01 % of Ba598Br had an inhibitory effect against acetylcholine (ACh, 10 μg/kg i.v.)-evoked bronchoconstriction. The effect of Ba598Br was more powerful and longer lasting than that of the same dose of atropine. Pretreatment with Ba598Br (0.3%) and atropine (0.3%) by inhalation produced a remarkable inhibitory effect on the asthmatic bronchoconstriction induced by inhalation of Ascaris swum antigen in naturally sensitized dogs. In this case, Ba598Br showed a potency of approx. twice that of atropine as estimated from the inhibitory percent. On the other hand, in the case of posttreatment (drugs being inhaled after the antigen inhalation), both drugs showed inhibitory effects of equal degree. As for the effects on increased airway secretion at the time of asthmatic attack, both drugs inhibited the excessive secretions without any remarkable change in the viscosity of the secretions. Inhalation of 0.3% Ba598Br showed a powerful antihistamine action with respect to histamine (Hist, 3 μg/kg i.v.)-induced bronchoconstriction after the bilateral cervical vagi and superior laryngeal nerves were amputated. However, almost no effect could be observed with the same dose of atropine. Both Ba598Br and atropine showed relaxing actions of the same degree against ACh contraction on the isolated canine trachea, bronchus and bronchiole preparations, with a particularly strong relaxation being observed in the bronchiole. On the other hand, Ba598Br showed relaxing actions against histamine-induced contractions, which were more powerful than those of atropine, in the bronchus and bronchiole. From the above findings, it is suggested that the Ba598Br inhalation brings about antiasthmatic effects by its persistent, powerful anticholinergic actions and its transient but powerful antihistamine actions.
  • Shiro NAKAIKE, Chizuko TANAKA, Naomi TOMITA, Mitsue UMEMOTO, Susumu OT ...
    1983 年 33 巻 5 号 p. 983-990
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    Effects of D-penicillamine-L-cysteine disulfide (P-C) on some immunological parameters were examined in normal and immunity-impaired mice and rats. P-C enhanced the DNA synthesis in concanavalin A-stimulated mouse spleen cell cultures in vitro. In vivo, administration of P-C produced either enhancement or depression of plaque forming cell (PFC) response and delayed type hypersensitivity (DTH) to sheep red blood cells (SRBC) in low responder mice to SRBC, depending on the dose of P-C. P-C restored the impaired PFC response in hydrocortisone-pretreated mice. The enhancing effect of P-C was not shown in high responder mice to SRBC, but an inhibiting effect was observed. P-C inhibited the suppressor cell induction on PFC response in mice immunized with a supraoptimum dose of antigen. In adjuvant arthritic rats, P-C induced severe arthritis by eliminating the suppressor cells regulating this disease process. The relevance of these findings and mode of action of D-penicillamine in rheumatoid arthritis is discussed.
  • Masato HIRATA, Tetsuaki INAMITSU
    1983 年 33 巻 5 号 p. 991-997
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    Fragmented sarcoplasmic reticulum fraction (SR) was prepared from the ventricle of canine heart, and the effect of diltiazem on its Ca2+ binding and Ca2+ release was examined by centrifugation and filtration methods using 45Ca. Cardiac SR bound 45-55 nmoles/mg of Ca ions in the presence of Mg-ATP. Diltiazem in concentrations up to 10-4 M had little effect on the Ca2+ binding of SR. The membrane of cardiac SR was “depolarized” by either changing propionate to chloride (anionic) or potassium to Tris (hydroxymethyl) aminomethane (Tris) (cationic). About 12% of the maximum Ca2+ bound to the SR was released by cationic “depolarization”, but no Ca2+ was released by anionic “clepolarization”. The Ca2+ release induced by the cationic “depolarization” was inhibited by diltiazem, and the inhibitory effect of diltiazem on the Ca2+ release was dependent on the incubation time. Incubation of the SR with 3×10-6 M diltiazem for 30 sec almost completely inhibited the release of Ca2+, while incubation with 3×10-7 M diltiazem incompletely inhibited the Ca2+ release. About 20% of the maximum Ca2+ bound to the SR was released by the addition of 5.1 mM caffeine. The Ca2+ release induced by caffeine was inhibited by increasing the concentration of MgCl2 from 5 to 10 mM, but was not inhibited by 10 mM procaine. An increase of ATP concentration accelerated the time course of the caffeine-induced release of Ca2+ from the SR and subsequent rebinding of Ca2+. Diltiazem up to 10-5 M had no effect on the caffeine-induced Ca2+ release. These findings clearly indicate that diltiazem inhibits the “depolarization”-induced Ca2+ release from cardiac sarcoplasmic reticulum.
  • Satoshi HASUMURA, Hitoshi ENDOW, Katsuhiko KAKUNO, Kazuo HOJO, Fuminor ...
    1983 年 33 巻 5 号 p. 999-1006
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    Cytochrome P-450 (P-450) content and laurate-ω-oxidation activity in rat kidney and liver microsomes were investigated following starvation. Multiple forms of P-450 were analyzed by one dimensional separation using peroxidase stained SDS-continuous gradient polyacrylamide gel electrophoresis. Gels of the hepatic microsomes treated with phenobarbital showed three P-450 bands, and the renal microsomes showed one sharp band, which was induced remarkably by starvation and coincided with the middle molecular form of P-450 from the hepatic microsomes. Since laurate-ω-oxidation activity was induced specifically by starvation but not by drug treatment, in both the kidney and the liver microsomes, the middle molecular form of P-450 might catalyze laurate-ω-oxidation. It seemed, therefore, that a special P-450 subunit catalyzing laurate-ω-oxidation has a greater function in the renal rather than hepatic microsomes because the specific laurate-ω-oxidation activity per starvation induced P-450 content was relatively similar in both the kidney and the liver.
  • Hiroyasu KINEMUCHI, Yumi SUNAMI, Toshihiko UEDA, Fumio MORIKAWA, Kazuy ...
    1983 年 33 巻 5 号 p. 1007-1015
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    The inhibitory effects of some detergents commonly used in biochemical research on carp liver mitochondrial monoamine oxidase were examined. Sodium dodecylsulfate, octyl-β-D-glucopyranoside, sodium cholate and Triton X-100 at relatively low concentrations caused strong dose-dependent inhibition of the activity towards tyramine, but digitonin caused only weak inhibition. Sodium dodecylsulfate, octyl-β-D-glucopyranoside and sodium cholate caused almost complete inhibition of activity in the concentration ranges tested. The extent of inhibition by Triton X-100 was greater after preincubation at 37°C for 30 min than that without preincubation, but with or without preincubation, the inhibition was not substrate-selective and was not complete at a relatively high concentration (2%) of Triton X-1 00. Without preincubation, the mode of inhibition by Triton X-100 was competitive and reversible with respect to the oxidations of 5-HT, tyramine and PEA, but after preincubation (37°C for 30 min), it became non-competitive and irreversible, depending on the concentration of detergent used. These findings suggest that it had different actions on the enzyme depending on preincubation. Triton X-100 also slightly changed enzyme sensitivity towards clorgyline and deprenyl, regardless of the preincubation time or the substrate used. Some possible mechanisms of the inhibitory effect of Triton X-100 are discussed.
  • Yutaka SAKAI
    1983 年 33 巻 5 号 p. 1017-1025
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    The pharmacological actions, in vivo, of estazolam and haloxazolam were comparatively studied. Spontaneous discharges of spinal motoneurons in cats were markedly suppressed by estazolam (3 mg/kg, i.d.), but unaffected by similarly administered haloxazolam. The facilitatory effect of stimulation of the posterior hypothalamus on the γ-activity was suppressed by both haloxazolam and estazolam (3 mg/kg, p.o., for each). The stimulus threshold was raised 1.7 times by haloxazolam and 1.6 times by estazolam. The facilitation of the γ-activity induced by stimulation of the mesencephalic reticular formation was also depressed by both drugs. The stimulus threshold was raised 6 times by estazolam, but unchanged by haloxazolam. The spinal monosynaptic reflex was unaffected by haloxazolam, while its amplitude was depressed to a half by estazolam (3 mg/kg, p.o., for each). The facilitation of the monosynaptic reflex induced by conditioning stimulation was depressed by both drugs (3 mg/kg, p.o.), but estazolam showed a stronger suppressive action. The seizure-like responses of spinal motoneurons, which were induced by stimulation of the gastrocnemius nerve following strychnine administration, were unaffected by 30 mg/kg of haloxazolam, while they were suppressed by estazolam of the same dose. Thus, the results of all experiments in the present study indicate that estazolam blocks the descending activating functions of both α- and γ-motor systems, whereas the blockade by haloxazolam is limited only to the γ-system, and also that the suppressive actions of estazolam on both α- and γ-motor systems are stronger than that of haloxazolam.
  • Noboru TODA, Masato YAMAMOTO
    1983 年 33 巻 5 号 p. 1027-1034
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    Angiotensin (ANG) II-induced relaxations in isolated dog renal and cerebral arteries are postulated to be mediated by the release of prostaglandin (PG) I2 from the arterial wall. In helical strips of dog renal arteries treated with dipyridamole, relaxations induced by ANG II (10-7 M) and exogenously applied PGI2 (10-8 M) were potentiated; the potentiation was appreciably greater in the ANG-induced relaxation. Treatment with phthalazinol did not alter the response to ANG II, but significantly potentiated the relaxation induced by PGI2. The ANG-induced relaxations were suppressed or reversed to contractions by aspirin or indomethacin. Combined treatment of dipyridamole with aspirin or indomethacin restored the relaxant response to ANG II, while phthalazinol in combination with aspirin did not restore the response. It may be concluded that the potentiation of responses to ANG II by dipyridamole is associated with increments in the release of PGI2 from the arterial wall and potentiations of the response of arterial smooth muscle to PGI2. Dipyridamole appears to increase the production of PGI2 even in the presence of PG synthesis inhibition by aspirin or indomethacin.
  • Keitaro HASHIMOTO, Toshiyuki SHIBUYA, Shoichi IMAI
    1983 年 33 巻 5 号 p. 1035-1039
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    Effects of an intravenous injection of indomethacin, prostaglandins (PGs) E1, E2 and F and prostacyclin were examined by the use of a model of two-stage coronary ligation arrhythmias in conscious dogs. Indomethacin had no effect on the arrhythmias occurring 48 hr after coronary ligation. PGs and prostacyclin were injected after the injection of indomethacin. PGs did not show any significant antiarrhythmic effects on the arrhythmias occurring 48 hr after coronary ligation, while prostacyclin showed a transient arrhythmogenic effect. From the foregoing results, both endogenous and exogenous PGs do not seem to play a significant role in the genesis of late coronary ligation arrhythmias in the dog.
  • Hisashi KURIBARA, Sakutaro TADOKORO
    1983 年 33 巻 5 号 p. 1041-1048
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    Effects of repeated administration of scopolamine at 0.5, 2.0 and 8.0 mg/kg s.c. on ambulatory activity in mice were investigated. The drug was administered 5 times at intervals of daily, 3-4 days and weekly. The ambulation-increasing effect of scopolamine progressively decreased when the mice were put into a tilting-type round activity cage of 25 cm in diameter and 1 3 cm in height during the presence of the acute drug effect. The tolerance, once produced, was maintained even 1 month after the withdrawal. In contrast, development of tolerance to the ambulation-increasing effect of scopolamine could not be found when the mice were put into a glass jar with a 5.5 cm diameter, in which the ambulation was perfectly restricted, after each drug administration. The present results suggest that the tolerance to the ambulation-increasing effect of scopolamine induced by repeated administration may be elicited by an interaction between the experimental situation and the drug effect.
  • Kyozo YAMANAKA, Shizuo YAMADA, Tadahiko OKADA, Eiichi HAYASHI
    1983 年 33 巻 5 号 p. 1049-1055
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    The effect of picrotoxin (PT) on catecholamine (CA) secretion was investigated in perfused bovine adrenal glands. A low dose of PT (3 μM) enhanced the CA secretion evoked by a 15-min exposure to 1, 1-dimethyl-4-phenylpiperazinium (DMPP, a nicotinic agonist; 0.1 mM), but a higher dose (0.3 mM) of PT inhibited the DMPP-evoked CA secretion. The rate of decline of secretory response to the prolonged DMPP stimulation was also accelerated by a higher dose (0.1 mM) of PT. In the dose-response curves for DMPP-evoked CA secretion, the inhibitory action of PT (0.3-1 mM) was more prominent at high doses than at low doses of DMPP. The inhibition pattern was similar to the pattern of a barbiturates blockade. In separate experiments, PT (0.1 mM) augmented calcium (10 mM) and high potassium (56 mM)-evoked secretory responses. Spontaneous CA secretion was unaffected by PT at the concentrations indicated above. These results indicate that a low dose of PT potentiates, but higher doses inhibit, the adrenal CA secretion by a nicotinic agonist and that the inhibitory effect of PT resembles that of barbiturates.
  • Hajime YASUHARA, Mayumi TONOOKA, Ikuho WADA, Katsuji OGUCHI, Koji SAKA ...
    1983 年 33 巻 5 号 p. 1057-1064
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    The relationship between the onset of hypertension and changes in monoamine oxidase (MAO) activity in the brains and hearts of spontaneously hypertensive rats (SHR) were studied. After 7-weeks-old, blood pressure of SHR increased rapidly and reached a level of 170 to 180 mmHg; but following 4 weeks of propranolol treatment (10 mg/kg/day), blood pressure decreased significantly compared to that of untreated SHR. Heart/body weights ratio of SHR was higher than that of normotensive Wistar Kyoto rats (WKY). MAO activities in the brain stem, the medulla oblongata and pons of the SHR were significantly higher than those in WKY at 7 weeks of age, and MAO activity in the brain stem of the propranolol-treated SHR was significantly lower than that in the untreated SHR. Propranolol inhibited MAO activity in brain tissue in vitro, and the 150 values of propranolol were identical (1×10-4 M) in SHR and WKY. In both the WKY strain and the SHR, the Vmax values of heart MAO increased with age, and the Vmax values of SHR were twice those of WKY. Km values for tyramine of heart MAO in WKY and SHR were approx. 100 μM and 140 μM, respectively; however, these values were not age-dependent. It was concluded that an increase in MAO activity in SHR brain stem may trigger a reduction in noradrenaline content and that propranolol may be responsible for its restoration, thus reducing peripheral sympathetic activity; moreover, the increase in MAO activity in the hearts of SHR may be of genetic origin.
  • Takashi MATSUBARA, Shigemi OTSUBO, Emiko YOSHIHARA
    1983 年 33 巻 5 号 p. 1065-1075
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
    Liver microsomal O-dealkylation activity was determined using O-methyl, O-ethyl and O-propyl derivatives of p-nitrophenol, 7-hydroxycoumarin (umbelliferon) and 7-hydroxyphenoxazone (resorufin) as substrates. Microsomal O-dealkylation activities of p-nitrophenol and 7-hydroxycoumarin O-alkyl derivatives were of similar levels, but the activities of 7-hydroxyphenoxazone O-alkyl derivatives were very low compared with those of other substrates. Pretreatment of rats with β-naphthoflavone resulted in the preferential increase of O-deethylation and O-depropylation activities regardless of the ring structure of the substrates, and the ratio of O-deethylation and O-depropylation activities to that of O-demethylation increased markedly. On the other hand, the O-dealkylase activity of all substrates increased generally upon pretreatment of the rats with phenobarbital, but the ratio of O-deethylase or O-depropylase activity to that of O-demethylase in the pretreated rats was not very different from that of the untreated animals. Hexobarbital inhibited competitively the O-dealkylation activity in control and phenobarbital-pretreated rat microsomes. On the other hand, the O-dealkylase activity in microsomes obtained from β-naphthoflavone-pretreated rats was inhibited remarkably by α-naphthoflavone, but not in microsomes prepared from untreated and phenobarbital-pretreated rats. Based on these results, this report discusses the relationship between the alteration of O-dealkylation activity and the composition change of cytochrome P-450 in microsomal membrane. Species differences in the substrate specificity of the O-dealkylation reaction and in the responsiveness of the animals to typical inducers were also observed using liver microsomes obtained from several animals under various conditions.
  • Nobuyuki SASAKAWA, Satoshi YAMAMOTO, Konosuke KUMAKURA, Ryuichi KATO
    1983 年 33 巻 5 号 p. 1077-1080
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
  • Chiaki KAMEI, Tatsuro DABASAKI, Kenji TASAKA
    1983 年 33 巻 5 号 p. 1081-1084
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
  • Atsuhiko KUBOTA, Masamichi SATOH, Hiroshi TAKAGI
    1983 年 33 巻 5 号 p. 1085-1088
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
  • Hiromichi TSURU, Tadao SHOJI, Tatsuro SHIGEI
    1983 年 33 巻 5 号 p. 1089-1091
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
  • Yasuyuki NOMURA
    1983 年 33 巻 5 号 p. 1092-1095
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
  • Hitoshi KONTANI, Ryozo KOSHIURA
    1983 年 33 巻 5 号 p. 1096-1099
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
  • Toshinori YAMAMOTO, Toru EGASHIRA, Yasumitsu YAMANAKA
    1983 年 33 巻 5 号 p. 1100-1103
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
  • Reiko IZUMI, Masakatsu TAKAHASHI, Hiroshi KANETO
    1983 年 33 巻 5 号 p. 1104-1106
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
  • Hiroshi KOGO, Masayuki SUMINO, Yoshio AIZAWA
    1983 年 33 巻 5 号 p. 1107-1110
    発行日: 1983年
    公開日: 2006/11/07
    ジャーナル フリー
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