The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 29, Issue 1
Displaying 1-21 of 21 articles from this issue
  • Koichiro TAKASAKI, Li Ching TANG, Masanobu URABE
    1979 Volume 29 Issue 1 Pages 1-7
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    In isolated splenic capsules of mouse, rat, guinea pig, rabbit, cat and dog, either a single or a cumulative dose of l-and dl-isoproterenol at a concentration higher than 10-9 M, induced a relaxation which was inhibited or blocked with pretreatment of 10-5 M propranolol. At a concentration of 5 × 10-6 M to 10-5 M l- and dl-isoproterenol, an inverse contraction was induced, and such response was prevented or reversed to one of relaxation in the presence of 10-5 M phentolamine. Application of 10-5 M epinephrine produced a strong contraction and such was reversed to one of relaxation after addition of 10-4 M phentolamine. This relaxation was reduced or blocked with pretreatment of 10-5 M propranolol. Thus, it was confirmed that both α- and β-receptors exist in the splenic capsule area of these different species.
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  • Michiko INOUE, Masako MORIKAWA, Minoru TSUBOI, Mamoru SUGIURA
    1979 Volume 29 Issue 1 Pages 9-16
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The ability of the esterase from intestine was studied for hydrolysis of estertype drugs during absorption. The intestinal esterase is present in the absorption sites in the intestine and hydrolyzes to a large extent during the absorption. In a study of the dietary effect on intestinal esterase, the esterase activity increased in rats fed a high-fat diet, decreased in those fasted or fed a fat-free diet, whereas the esterase activity in the rat treated with phenobarbital showed no marked change. Thus the esterase from intestinal mucosa appears to be characteristically quite different from hepatic esterase. The esterase from human intestine was characterized and compared with esterase from rats, mice, rabbits, guinea pigs and dogs. There was a difference in the substrate specificity of the esterase and there were significant species differences in the electrophoretic behavior of the enzyme among the species tested. These results indicate that intestinal esterase from humans differs characteristically from esterases in experimental animals.
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  • Michiko INOUE, Masako MORIKAWA, Minoru TSUBOI, Takashi YAMADA, Mamoru ...
    1979 Volume 29 Issue 1 Pages 17-25
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Esterase from human intestinal mucosa was purified 210 fold by solubilization with Triton X-100, chromatography on DEAF-cellulose, Sephadex G-100 and hydroxylapatite, and isoelectric focusing. The purified esterase showed a single band by polyacrylamide gel electrophoresis. The molecular weight of the purified esterase was estimated to be about 55, 000 by gel filtration on Sephadex G-150, and the isoelectric point was 5.02. The purified esterase was strongly inhibited by diethyl p-nitrophenyl phosphate (E-600) and diisopropyl fluorophosphate (DFP), and was not inhibited by eserine sulfate and p-chloromercuribenzoate. The purified esterase from human intestinal mucosa was found to be one of the carboxylesterases. The purified esterase hydrolyzed ester-type drugs, i.e., aspirin, clofibrate, indanyl carbenicillin and procaine, but did not hydrolyze amide-type drugs and choline-type drugs.
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  • Katsuo KAMATA, Minoru WATANABE, Yutaka KASUYA
    1979 Volume 29 Issue 1 Pages 27-32
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Continuous rhythmic contractions were observed in longitudinal muscle strips of fundus obtained from the chronically vagotomized rat stomach. These vagotomy-induced rhythmic contractions (VRC) were not blocked either by tetrodotoxin (3 × 10-6 M) or atropine (3 × 10-7 M), indicating that the VRC was myogenic in origin. It was also found that the VRC had the following characteristics. 1) The VRC was blocked either by 10-5 M D600 or by Ca2+ deprivation from the medium. 2) On replacement of Na+ with sucrose or of K+ with Na+, the tone of fundus strips was concomitantly elevated with the cessation of the VRC. 3) 10-5 M ouabain blocked the VRC. 4) The VRC was blocked by cooling. 5) The VRC disappeared under anoxic conditions. Based on these results possible mechanisms of the VRC are discussed in relation to an energy dependent activity of the cell membrane.
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  • Kiyoshi KIMURA, Yutaka KIMURA, Katsuya OHATA, Hiroshi TAKAGI
    1979 Volume 29 Issue 1 Pages 33-39
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of intraventricularly administered serotonin (5HT), noradrenaline (NA), dopamine (DA) and metaraminol on the reserpine-induced spikes recorded from the medial nucleus Trapezoides (Trap. m.) in rabbits were investigated. 5HT (30, 50 μg) produced marked decreases in the amplitude and discharge rate of the spikes 3 to 5 min after intraventricular administration. NA (30, 50 μg) also produced similar effects to those of 5HT, but DA at the same dosage produced no significant changes in the amplitude and discharge rate of spikes. Metaraminol, a metabolite of α-methyl-mtyrosine, produced gradual and long-lasting, potent suppression of spikes. Ninety min later, spikes were completely suppressed, and no recovery was observed within 6 hours after intraventricular administration. These results indicate that NA has a similar suppressing action to that of 5HT on the generation of the reserpine-induced spikes.
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  • Kiyoe KIM, Yoshihisa KUDO, Hideomi FUKUDA
    1979 Volume 29 Issue 1 Pages 41-48
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The propriospinal motor function of the frog spinal cord was investigated pharmacologically in the isolated spinal cord-nerve-muscle preparation. In the preparation with a pair of antagonistic muscles, the tissues showed reciprocal contractions in response to the spontaneous discharges from the ventral root. M. tibialis anterior responded to the discharges from the ventral root and showed slow contractions. Contractions of the m. gastrocnemius were much less frequent but the movement was rapid and strong. The addition of acetylcholine (10-4-10-3 M) to the medium, perfusing the spinal cord, resulted in a predominant excitation of m. tibialis anterior. Carbamylcholine (10-5 M) and bethanechol (10-4 M) induced rhythmical contractions in m. tibialis anterior and depressed the movement of m. gastrocnemius. These effects were blocked by atropine (10-5 M). Serotonin (10-5 M) exerted a strong facilitatory effect on both muscles which contracted reciprocally during this treatment. L-Glutamate (10-4-10-3 M) induced a transient synchronous contraction in both muscles. By means of the sucrose-gap method, cholinomimetics and serotonin proved to have no direct effect on the motoneuron, while L-glutamate had a direct effect. Results suggest that propriospinal controlling mechanisms, regulated via serotonergic and cholinergic pathways exist and drive co-ordinate muscle movement.
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  • Hikaru SUZUKI, Yushi ITO, Hirosi KURIYAMA, Takio SHIMAMOTO
    1979 Volume 29 Issue 1 Pages 49-58
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of phthalazinol, EG 626, on the membrane and mechanical properties of the vascular smooth muscles, namely superior mesenteric artery and main pulmonary artery of the rabbit were examined. EG 626 (10-7-3 × l0-5 g/ml) did not modify the membrane potential (-56.5 nmV), length constant of the tissue (1.47 mm), and rectifying property of the membrane in the pulmonary artery. The membrane potential of the mesenteric artery (-59.8 mV) was also not modified. By treatment with 10-5 g/ml EG 626, the mechanical responses of both muscle tissues induced by either direct muscle stimulation (1 sec pulse) or by nerve stimulation (0.5 msec, 30 Hz) were suppressed. The mechanical response induced by nerve stimulation was more dominantly suppressed than that induced by direct muscle stimulation. Dose-response curve obtained from the relation between noradrenaline and mechanical response in both pulmonary and mesenteric arteries shifted to the right by treatment with 10-5 g/ml EG 626. When the depolarization-contraction relationship was observed before and during application of EG 626 (10-5 g/ml), using the voltage clamp technique, the application of this agent raised the mechanical threshold to evoke contraction and amplitude of the contraction evoked at any given grade of depolarization was consistently reduced as compared with that evoked in Krebs Solution. These observations suggest that EG 626 suppresses the mobilization of Ca++ during contraction and also the release of chemical transmitter from the nerve terminals by suppression of Ca++ mobilization. EG 626 would thus appear to act on the vascular smooth muscles as a vasodilator.
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  • Yoshiko MORITA, Kuniko KOYAMA
    1979 Volume 29 Issue 1 Pages 59-65
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Concentration of adrenocorticotropic hormone (ACTH) in the serum increased and reached the maximum level 10 min after the injection of histamine (dihydrochloride, 0.5 or 1 mg/100 g) i.p. into rats. The maximum concentration of ACTH in the serum was dependent on the dose of histamine. The ACTH concentration then decreased and was close to the normal level 30 to 60 min after the injection. The ACTH secretion induced by histamine (0.5 mg/100 g) was inhibited completely by the pretreatment with the antagonists of H1-receptor, diphenhydramine (hydrochloride, 0.2-0.5 mg/100 g), promethazine (hydrochloride, 0.1-0.2 mg/100 g) and d-chlorpheniramine (maleate, 0.02-0.05 mg/ 100 g). The antagonist of H2-receptor, metiamide (2-4 mg/100 g) inhibited the ACTH secretion significantly but not completely. These results suggest that H1-receptor plays a major role in the histamine-induced ACTH secretion, although H2-receptor is also involved in this ACTH secretion.
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  • Kazuhiro GOTO, Masao HISADOME, Hiroshi IMAMURA
    1979 Volume 29 Issue 1 Pages 67-75
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Intraperitoneal administration of carrageenin-zymosan suspension into rats induced an increment of the free activity and its ratio of aryl sulfatase in the exudate and such was accompanied by protein exudation and polymorphonuclear leukocyte emigration. Each test solution was orally administered twice, 1 hr before and 2 hr after, or once 2 hr after injection of the irritant. The peritoneal fluid was withdrawn 5 hr after the injection. 2-{4-(2-Imidazo[l, 2-a]pyridyl)phenyl} propionic acid (Y-9213) and other anti-inflammatory drugs tested inhibited the increment of the ratio of the free activity (aryl sulfatase) in the peritoneal fluid at the same dose which showed anti-inflammatory activities such as prevention of protein exudation. These results suggest that Y-9213 inhibits the phagocytic secretion in vivo of lysosomal constituents from leukocytes.
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  • Hiroaki NISHIO, Tomio SEGAWA, Hiroshi TAKAGI
    1979 Volume 29 Issue 1 Pages 77-86
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    When utilizing a cold treatment we found that uptake activity of 5-hydroxytryptamine (5HT) by blood platelets of the rabbit was decreased in a non-competitive manner, while endogenous 5HT concentration of the platelets and the platelet counts were not affected. Morphologically, the cold treatment induced a dissociation and disappearance of circumferential bands of microtubules (CB-Mt) and the platelets, protruding pseudopods, lost their discoidal shape. Incubation of platelets with colchicine or vinblastine provided similar morphological alterations of CB-Mt, but there was only a slight inhibition toward the 5HT uptake, a finding which indicated that CB-Mt of platelets do not play an essential role in the 5HT uptake system of platelets. The decreased 5HT uptake by the cold treatment was sharply restored by addition of theophylline to the medium, but not by dibutyryl cyclic AMP. The former also significantly enhanced the 5HT uptake by the intact platelets, and this effect was potentiated by prostaglandin E1 (PG-E1), but not by prostaglandin E2 (PG-E2). The possibility is raised that only endogenous cyclic AMP may regulate the 5HT uptake system of platelets. Pluronic F68, non-ionic detergent, had no effect on 5HT uptake by the intact platelets but stimulated the effect of the cold treatment, probably through facilitating conformational change of membrane induced by the treatment.
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  • Hideyasu YAMAUCHI, Tadashi ISO, Heitaroh IWATA
    1979 Volume 29 Issue 1 Pages 87-92
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Anti-inflammatory and systemic immunosuppressive effects of topically applied steroidal and nonsteroidal anti-inflammatory agents on experimental immunogenic uveitis in rabbits were studied. The onset of the immunogenic uveitis induced by a single intravitreous injection of bovine serum albumin (BSA) was significantly correlated with the appearance of anti-BSA antibody in the serum. A significant correlation was also found between the maximum serum level of antibody and the maximum severity of uveitis. Suspensions of fluorometholone, dexamethasone or indomethacin were applied topically twice a day for a month to eyes injected with BSA. Ocular inflammation was suppressed by fluorometholone and dexamethasone, fluorometholone having the greater anti-inflammatory activity. The circulating antibody titer was also suppressed by both these steroids, but conversely fluorometholone had the lower systemic immunosuppressive activity. Indomethacin did not suppress the uveitis or circulating antibody production. The results of these investigations indicate that the anti-inflammatory effect of the steroid fluorometholone surpasses the immunosuppressive effect, unlike usual anti-inflammatory steroids.
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  • Hiroshi WATANABE, Kazuo WATANABE
    1979 Volume 29 Issue 1 Pages 93-104
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Electrolytic lesion in combination with 6-hydroxydopamine (6-OHDA) microinjection was produced in rat substantia nigra (SN) and the animals were observed for drug-induced rotational behaviour. Apornorphine produced rotation toward the left (contralateral) while methamphetamine produced totation toward the right (ipsilateral) in rats with 6-OHDA lesion of the right SN. Both apomorphine and methamphetamine produced rotations ipsilateral to the side of the lesion in rats with unilateral electrolytic lesion of the SN. When the electrolytic lesion was placed in the right SN in an animal that had been treated with 6-OHDA (group 3), apomorphineinduced rotation toward the left was markedly suppressed. Methamphetamine-induced rotation was not affected by this treatment. When the electrolytic lesion was placed in the left SN of rats with 6-OHDA lesion of the right SN (group 4), apomorphineinduced rotation toward the left was significantly enhanced. Methamphetamineinduced rotation obviously decreased. The results in group 3 indicate that electrolytic lesion may induce a dysfunction of postsynaptic factors (i.e. efferent pathways and dopamine receptors) in addition to the degeneration of the nigrostriatal dopaminergic pathway, which may indicate a difference in the direction of apomorphine-induced rotation in groups 1 and 2. The enhancement of rotation produced by apomorphine in group 4 appears to be the result of a dysfunction of the postsynaptic factors in the left SN in combination with the denervation supersensitivity to apomorphine in the right striatum.
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  • Ryozo OISHI, Shigenori WATANABE, Kenji OHMORI, Shigenobu SHIBATA, Show ...
    1979 Volume 29 Issue 1 Pages 105-111
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of stimulation of the locus coeruleus (LC) on evoked potential in the medial amygdala elicited by stimulation of the olfactory bulb (OB-AME potential) were studied in gallamine-immobilized rats. The amplitude of the OB-AME potential was inhibited 27.5%. by the conditioning stimulation of LC delivered 30 msec before the test stimulation. The inhibitory effect of LC was reduced by propranolol 5 mg/kg i.p., but not by phentolamine 10 mg/kg i.p.. This effect was also reduced by tetrabenazine 10 mg/kg i.p.. Methamphetamine 5 mg/kg i.p. produced considerable potentiation of the LC inhibitory effect and a reduction of the OB-AME potential itself. These results suggest that the LC plays an inhibitory role in the electrical activity of the medial amygdala.
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  • Tokihito YUKIMURA, Masahito IMANISHI, Youichi ABE, Kenjiro YAMAMOTO
    1979 Volume 29 Issue 1 Pages 113-123
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Metolazone, the sulfonamide diuretic was investigated to determine the sites of action. We used a radioactive microsphere, clearance and stop-flow method in anesthetized dogs. Urine flow and urinary excretion of sodium and potassium were increased at 5-60 min when metolazone was given intravenously at doses of 0.2-5.0 mg/kg, while total renal blood flow, distribution of cortical renal blood flow and GFR did not change. The urinary excretion rate of sodium to potassium (Na/K) increased from 5.69±0.82 to 8.07±0.76 in a dose of 1.0 mg/kg, i.v. Osmolar clearance and free water reabsorption increased almost proportionally, indicating that metolazone has little effect on the medullary portion of the ascending limb of Henle and may have a proximal site of action. In stop-flow experiments, a significantly raised U/PNa/U/Pcreatinine was observed at the dip situated distally to the ascending limb of Henle. These findings indicate that the diuretic action of metolazone may be due to the inhibition of sodium reabsorption in the distal nephron segments, in addition to the absence of modification of the cortical regional blood flow.
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  • Matao SAKANASHI, Ichiya HIRAKI
    1979 Volume 29 Issue 1 Pages 125-131
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of vasodilating drugs on microcirculation of the rat cremaster muscle were investigated microscopically. Topical application and intravenous injection of papaverine produced dilatation of arterioles. Cyclandelate applied topically dilated the arterioles to a considerable extent. Topical application of bamethan induced arteriolar dilatation while bamethan given intravenously constricted the arterioles. Kallikrein applied topically induced a slight dilatation of arterioles, and intravenous administration of kallikrein produced an appreciable vasodilatation. Topical administration of bradykinin produced a vasodilatation of arterioles of the rat cremaster muscle. These results indicate that direct action of a drug on the microcirculation can be properly evaluated by the microscopic method in the rat cremaster muscle, if the drug is applied topically, in the vicinity of small vessels under study.
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  • Takushi X. WATANABE, Hirofumi SOKABE
    1979 Volume 29 Issue 1 Pages 133-135
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Kazunobu SUGAWARA, Naoko TAKAMI, Masayori OZAKI
    1979 Volume 29 Issue 1 Pages 135-138
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Fumitake IKEDA, Yasuo IKEDA, Chiyoko INAGAKI, Shuji TAKAORI
    1979 Volume 29 Issue 1 Pages 138-141
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Michio YAJIMA, Kazumi TAKEYA
    1979 Volume 29 Issue 1 Pages 141-144
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Shin-ichi AKIYAMA, Hideki IGISU
    1979 Volume 29 Issue 1 Pages 144-146
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Chen-Road HUNG, Susumu OKABE, Yutaka KASUYA
    1979 Volume 29 Issue 1 Pages 147-150
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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