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Teruyuki YANAGISAWA, Keisuke SATOH, Norio TAIRA
1979 Volume 29 Issue 5 Pages
687-694
Published: 1979
Released on J-STAGE: December 19, 2006
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The mechanism of action of 2-nicotinamidoethyl nitrate (SG-75), was investigated by the use of arterially blood-perfused papillary muscle preparations of the dog. All drugs were administered intra-arterially. SG-75 shortened the effective refractory period (ERP) and decreased the rate of automaticity and developed tension of the papillary muscle, whereas verapamil failed to change the ERP despite a decrease in the developed tension. SG-75 in extremely high doses induced ventricular fibrillation. Methacholine produced decreases in the rate of automaticity and developed tension, and the actions were abolished by atropine. The SG-75-induced decreases in two parameters were not modified by atropine. These results indicate that the cardiac action of SG-75 differs from that of calcium-antagonistic vasodilators and it is suggested that the basic mechanism of action of SG-75 involves an increase in potassium conductance in the membrane of cardiac muscle, without mediation through muscarinic receptors.
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Hiroaki TSUKATANI, Sadaji YAMADA, Akira TOKUMURA, Takafumi ITAMI
1979 Volume 29 Issue 5 Pages
695-705
Published: 1979
Released on J-STAGE: December 19, 2006
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Effects of “Depressor-I” (D-I), a new hypotensive phospholipid obtained from bovine brain lipid fraction, on systemic arterial blood pressure were investigated. The hypotensive activity of D-I in urethane anaesthetized rats was dose dependent and tachyphylaxis and/or sensitization were not observed. Increments of the respiration and the heart rate were observed with sharp falls in blood pressures following intravenous administration of D-I, in simultaneous recordings in anaesthetized rats. D-I elicited hypotension in all species of animals examined, and the sensitivities to D-I were much the same, however, there were two types in patterns of duration on responses and the durations were also dose dependent. D-I exhibited depressor-responses even in conscious rats, though responses were much smaller compared with those seen in anaesthetized rats. In a comparison of anaesthetic agents in rats, the highest hypotensive activity of D-I was observed with pentobarbital anaesthesia, a moderate response was seen with α-chloralose and the least response was seen with urethane. In spinal rats or those pretreated with reserpine or antagonists, such as atropine, diphenhydramine, propranolol and hexamethonium, D-I also elicited hypotension. These results suggest that “Depressor-I” does not elicit the depressor action via the stimulation of the central and the autonomic nervous systems but rather by a direct action on peripheral blood vessels.
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Takao KOMABAYASHI, Seiya SAKAMOTO, Minoru TSUBOI
1979 Volume 29 Issue 5 Pages
707-713
Published: 1979
Released on J-STAGE: December 19, 2006
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Oxygen uptake and amylase output in rat submandibular gland slices were measured by utilizing adrenergic agonists. Adrenaline, noradrenaline and isoproterenol significantly stimulated the oxygen uptake and amylase output. In the presence of propranolol or phenoxybenzamine, adrenaline-stimulated oxygen uptake was obviously blocked. Adrenaline-stimulated amylase output was inhibited by propranolol, but was not inhibited by phenoxybenzamine. The increase in oxygen uptake by noradrenaline was blocked by phenoxybenzamine, but not by propranolol. Isoproterenol-stimulated oxygen uptake and amylase output were strongly inhibited by propranolol. The oxygen uptake due to isoproterenol was little affected by phenoxy-benzamine. These results suggest that the increase in oxygen uptake seen with adrenergic agonists is mediated by both α- and β-receptors, and that the amylase output is evoked through the stimulation of β-receptors.
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Yasushi YAMAZOE, Masahiko SUGIURA, Tetsuya KAMATAKI, Ryuichi KATO
1979 Volume 29 Issue 5 Pages
715-721
Published: 1979
Released on J-STAGE: December 19, 2006
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Carbon monoxide inhibited the carbon tetrachloride-induced NADPH oxidation rate. The addition of methylviologen to the incubation mixture under the atmosphere of nitrogen resulted in the enhancement of the reductase activity of microsomes for carbon tetrachloride, as determined by chloroform formation. The addition of methylviologen also enhanced the carbon tetrachloride-induced loss of cytochrome P-450, while the apparent content of cytochrome b
5 and the activity of NADPH-cytochrome
c reductase remained unchanged. Under a strong inhibition of lipid peroxidation by addition of EDTA, carbon tetrachloride induced a clear loss of cytochrome P-450 to the extent similar to that seen in the absence of EDTA. These results indicate that cytochrome P-450 is directly degraded in association with the reductive metabolism of carbon tetrachloride by cytochrome P-450.
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Kyoichi KAGAWA, Setsuo TOMIZAWA
1979 Volume 29 Issue 5 Pages
723-731
Published: 1979
Released on J-STAGE: December 19, 2006
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Liver subcellular distributions of three different dextran sulfates (DSs) with average molecular weight (AMW) of 3000, 20, 000 and 200, 000, and sulfur content of 18%, anticoagulants and antilipemic agents, were examined in rats after intravenous administration of 50 mg/kg. About 20% of the injected radioactivity was taken up by liver 15 min-3 hr after
35S-DS administration, but the uptake of
35S-DS with AMW of 200, 000 was slower than that of the other DSs. About half of the radioactivity distributed in livers was found in the cytosol fraction. The cytosol fraction/liver ratio of the radioactivity gradually decreased with the increase in the nuclear fraction/liver ratio. The specific radioactivity of the lysosomal fraction was 5-20 times as large as that of the other fractions. Unchanged forms of
35S-DSs with AMW of 3000 and 20, 000 were found in the lysosomal and the cytosol fractions. Administration of DSs with AMW of 20, 000 and 200, 000 significantly enhanced the Na
+-K
+-dependent ATPase activity of lysosomal fraction which has been considered to be an index of endocytosis. These findings suggest that DSs are probably transferred into liver cells by transmembrane and endocytotic transports.
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Hisashi KURIKI, Taketoshi SAIJO, Yasuko ASHIDA, Yoshitaka MAKI
1979 Volume 29 Issue 5 Pages
733-744
Published: 1979
Released on J-STAGE: December 19, 2006
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Effects of 6-ethyl-3-(1
H-tetrazol-5-yl)chromone (AA-344) on the experimental models of the type I-IV allergic reactions were studied in comparison with those of disodium cromoglycate (DSCG), dexamethasone and other agents. AA-344 showed inhibitory effects on the homologous passive cutaneous anaphylaxis and the passive systemic anaphylaxis in guinea pigs. However, it had only a slight or little effect on the Forssman shock in guinea pigs, the complement-dependent cytolysis of mast cells in rats, the Arthus reaction in guinea pigs and the tuberculin reaction and the contact sensitivity in mice. DSCG was less effective, using these experimental models. Dexamethasone showed a suppressive effect on the type III and IV allergic reactions. The results indicate that AA-344 selectively suppresses the type I allergic reaction.
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Chieko KOHDA, Munekazu GEMBA
1979 Volume 29 Issue 5 Pages
745-751
Published: 1979
Released on J-STAGE: December 19, 2006
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The effect of verapamil on Ca
2+ and Mg
2+ accumulation was investigated in isolated rat kidney cortex mitochondria. For the 50% inhibition of Ca
2+ accumulation, 2×10
-4 M verapamil concentration was required in the presence of ATP (2 mM) and phosphate (5 mM). Omission of phosphate from the medium increased the inhibitory effect of verapamil on Ca
2+ accumulation. Verapamil had no effect on Ca
2+ accumulation in the presence of both ATP and succinate (7.8 mM), but further addition of phosphate resulted in a significant inhibition of Ca
2+ accumulation by verapamil. Mg
2+ accumulation of mitochondria was similarly depressed by verapamil. The same tendency was found as for the modification of verapamil effect by acetate in mitochondrial Ca
2+ and Mg
2+ accumulation. Succinate oxidation of mitochondria was not affected by verapamil in the absence of phosphate, but was inhibited by verapamil in the presence of phosphate. Therefore, it seemed reasonable to assume that the depression of Ca
2+ and Mg
2+ transport of mitochondria by verapamil is modulated by permeant anions.
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Saizo YANAURA, Tsutomu SUZUKI
1979 Volume 29 Issue 5 Pages
753-762
Published: 1979
Released on J-STAGE: December 19, 2006
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To analyze the drug ingestion patterns of rats in the course of dependence development while on the drug-admixed food (DAF) method, an automatic food intake measuring apparatus was developed. Rats were put on morphine-admixed food, and the food ingestion patterns were recorded with the apparatus in the course of dependence development, during drug withdrawal and at the time of challenge with levallorphan. The naive rats ate the regular diet intermittently at night, and the eating time of morphine-treated rats was longer than that of naive rats. The treated rats also exhibited a frequent eating behavior after 4-5 days on the morphine treatment. During morphine withdrawal, the animal gradually ate the regular diet at about 1-hour intervals, even after evolvement of abstinence signs. When the morphine-dependent rats were given levallorphan, they neither ate nor approached to the food for the first 2-3 hours, but after this time, showed abrupt increases in these activities. Thus, the drug intake pattern of rats in the course of morphine dependence development suggests a correlation between the stage of development of physical dependence and the stage when the animals frequently eat the drug-admixed food.
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Kazushi KUSHIKU, Seiichi ICHIMASA, Hiro-o KAMIYA, Tatsuo FURUKAWA
1979 Volume 29 Issue 5 Pages
763-774
Published: 1979
Released on J-STAGE: December 19, 2006
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The relative contribution of nicotinic and muscarinic receptors to the cholinergic transmission of the inferior mesenteric ganglion was studied in spinal dogs by recording changes in perfusion pressure of the inferior mesenteric artery as an indicator of ganglionic function. Preganglionic stimulation elicited a frequency (2.5-320 Hz)-dependent rise in the perfusion pressure, which was inhibited by i.v. hexamethonium (C
6) (10 mg/kg) or atropine (0.1 mg/kg) administered after C
6. Acetylcholine (ACh) (0.1-1000 μg) administered into the inferior mesenteric artery to reach the mesenteric ganglion induced a dose-dependent rise in perfusion pressure and this dose-response curve was shifted to the right by C
6 or atropine. Bethanechol (1-1000 μg) i.a. produced a dose-dependent rise in the pressure, which was abolished after i.v. atropine. Tetramethylammonium (1-300 μg) i.a. elicited an increase in the pressure though the effects were decreased at larger doses, and these effects were strongly inhibited by i.v. C
6. ACh (5-1000 μg) administered into the right subclavian artery to reach the cardiac sympathetic ganglia caused a dose-dependent positive chronotropic effect, which was inhibited by i.a. C
6 or atropine. The results suggest that the inferior mesenteric ganglion seems to differ from the cardiac ganglia in relative contribution of nicotinic and muscarinic receptors to the cholinergic transmission.
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Tetsuro URUSHIDANI, Yutaka KASUYA, Susumu OKABE
1979 Volume 29 Issue 5 Pages
775-780
Published: 1979
Released on J-STAGE: December 19, 2006
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Bilateral adrenalectomy markedly aggravated gastric ulcers in rats induced by 5 or 20 mg/kg of indomethacin. The degree of aggravation was much the same in experiments done 1 and 14 days after operation. Pretreatment with prednisolone 10 mg/kg or cortisone acetate 10 mg/kg given subcutaneously significantly suppressed the aggravated ulceration in response to 20 mg/kg of indomethacin in these adrenalectomized rats. Desoxycorticosterone acetate 10 mg/kg, however, had no effect on the aggravation of indomethacin-induced ulcers. Epinephrine 0.1 or 1 mg/kg given subcutaneously markedly suppressed the indomethacin-induced ulcers in adrenalectomized rats. Removal of the adrenal medulla alone did not appreciably influence the development of indomethacin-induced ulcers. These results indicate that the adrenal cortex, particularly the area containing glucocorticoids, plays an important role in suppression of the noxious effect of indomethacin on the rat gastric mucosa.
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Nobuyoshi YOSHIDA, Chikako TANAKA, Kohtaro TANIYAMA, Makoto KONDO
1979 Volume 29 Issue 5 Pages
781-787
Published: 1979
Released on J-STAGE: December 19, 2006
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Age-related changes in cyclic adenosine 3', 5'-monophosphate levels in response to norepinephrine (NE) in the rectum of postnatal rats and the localization of cyclic AMP in the rectum were studied. During the first 2 weeks after birth, the basal levels of cyclic AMP were high, NE responses to cyclic AMP contents were minimal and thereafter, the basal cyclic AMP levels rapidly declined, while NE response significantly increased compared to those seen in tissues from adult rats. Furthermore, cyclic AMP immunofluorescence was visualized in smooth muscle and postganglionic neurons of the myenteric plexus. NE application produced an increase of cyclic AMP immunofluorescence in smooth muscle. These results indicate that NE response to cyclic AMP levels in rat rectum is age-dependent and suggest that the majority of β-adrenoceptors associated with cyclic AMP generating system are localized in the smooth muscle of rat rectum.
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L.H. WANG FU, Noboru TODA
1979 Volume 29 Issue 5 Pages
789-796
Published: 1979
Released on J-STAGE: December 19, 2006
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In helically-cut strips of cerebral arteries isolated from dogs, analogues of 5-hydroxykynurenamine (5-HK), including 2-(3'-aminopropyl)-aniline (Cpd. 1), 2'-amino-3-dimethylamino-3'-hydroxypropiophenone(Cpd. II), 2'-amino-3-dimethylamino-5'-hydroxypropiophenone (Cpd. III) and 2', 3-diamino-propiophenone (kynurenamine), caused a dose-related contraction which was antagonized by treatment with methysergide. The potency for inducing contractions was in the order of 5-hydroxy-tryptamine>5-HK>Cpd. III>kynurenamine, Cpd. I and Cpd. 11. Treatment with the 5-HK analogues antagonized the contractile response to 5-hydroxytryptamine in a dose-dependent manner, the antagonistic potency being in the order of 5-HK>Cpd. III>kynurenamine, Cpd. II>Cpd. I. Alterations in the hydroxy group on the benzene ring and/or radicals of long side chain of 5-HK attenuated the agonistic and antagonistic actions of 5-HK; however, the attenuation of these actions differed. Thus, the radicals appear to be involved in the agonistic and antagonistic actions to a different extent.
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Norifumi YONEHARA, Kihachi SAITO, Shuji UCHIDA, Yutaka NOGUCHI, Hirosh ...
1979 Volume 29 Issue 5 Pages
797-799
Published: 1979
Released on J-STAGE: December 19, 2006
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Tsutomu NOHNO
1979 Volume 29 Issue 5 Pages
800-803
Published: 1979
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Hirohito SHIOMI, Hajime NAKAHARA, Mitsuru SEGAWA, Hiroshi TAKAGI
1979 Volume 29 Issue 5 Pages
803-806
Published: 1979
Released on J-STAGE: December 19, 2006
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Akira ISHIBASHI, Yutaka KASUYA, Koji TAKEUCHI, Susumu OKABE
1979 Volume 29 Issue 5 Pages
807-811
Published: 1979
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Keiji KOMORIYA, Hitoshi OHMORI, Akiko AZUMA, Seizi KUROZUMI, Yoshinobu ...
1979 Volume 29 Issue 5 Pages
811-813
Published: 1979
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Kazuyoshi HORISAKA, Kazuko WATANABE
1979 Volume 29 Issue 5 Pages
814-816
Published: 1979
Released on J-STAGE: December 19, 2006
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Masaatsu UCHIDA
1979 Volume 29 Issue 5 Pages
817-820
Published: 1979
Released on J-STAGE: December 19, 2006
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