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Volume 93 (1989)
- Issue 6 Pages 315-
- Issue 5 Pages 271-
- Issue 4 Pages 203-
- Issue 3 Pages 89-
- Issue 2 Pages 29-
- Issue 1 Pages 7-
Volume 93, Issue 3
Displaying 1-11 of 11 articles from this issue
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Hirosi KURIYAMA1989 Volume 93 Issue 3 Pages 89-101
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSAs a pharmacological tool, drug actions on the K- or agonist-induced contraction of smooth muscle tissues are commonly investigated. However, underlying mechanisms for generation of these contractions are not yet completely clarified. For example, the high K-induced contraction was thought to be evoked by influx of Ca during activation of the voltage dependent Ca channel in the sarcolemma and also subsequent release of Ca from the sarcoplasmic reticulum. However, investigations of the voltage dependent Ca channel using the whole cell voltage and patch clamp procedures suggested that influx of Ca occurred with short period during the depolarization, mainly due to the occurrence of inactivation of the Ca channel. On the other hand, the amount of Ca in the cytosol remained high during the depolarization, as estimated using aequorin or fura-2. The agonist-induced contraction was thought to be evoked by influx of Ca by activation of the receptor activated Ca channel with subsequently activated voltage dependent Ca channel (either lowering the threshold or as a consequence of the depolarization), and release of Ca from the sarcoplasmic reticulum following synthesis of second messengers. However, detailed mechanisms are not yet completely understand. Present knowledge concerning underlying mechanisms of the K- and agonist-induced contractions are discussed.View full abstractDownload PDF (9579K) -
Satoru SUNANO1989 Volume 93 Issue 3 Pages 103-112
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSVanadate, a trace element of biological tissues and fluid, has been known to be a potent inhibitor of Na, K-ATPase in various tissues. In skeletal muscle, it inhibits the Na, K-ATPase of the membrane fraction, whereas it can not inhibit the Na, K-pump in an intact preparation. It inhibits the Ca-ATPase of the sarcoplasmic reticulum and that of contractile proteins. Vanadate potentiates the contraction of some heart muscles, while it depresses the contraction in some other heart muscles. The positive and negative inotropic effects are mediated by changes in the action potential. The inhibition of Na, K-ATPase is not always involved in the inotropic actions. The inhibition of the Ca-ATPase of the sarcoplasmic reticulum and plasma membrane can be the causes of positive inotropic action. Actions on adenylate cyclase can also be the cause of inotropism. In smooth muscle, vanadate induces contractions with and/or without membrane excitation. The contractions are initiated by both the influx of extracellular Ca2+ and the release of intracellular bound Ca2+. The inhibition of Na, K-ATPase is not involved in the contraction but the inhibition of the Ca-pump of membranous systems can be the cause of the contraction. Vanadate is a useful tool for studies on the excitation-contraction coupling in muscles.View full abstractDownload PDF (8676K) -
Takeshi OMATA, Hajime INOUE, Yoshiyuki SEYAMA, Saburo YAMASHITA1989 Volume 93 Issue 3 Pages 113-118
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSChanges in the contents of various amines and histidine decarboxylase (HDC) activity in the gastric mucosa during the healing process of acetic acid induced gastric ulcer in rats were sequentially examined in the ulcer region and intact region at 2, 10, 40, 80, 180 and 365 days after the operation. The following results were obtained: 1) Histamine (HA) content in the ulcer region was decreased as compared with the intact region at 2 and 10 days and returned to the control level in 40 days. After 180 days, the contents in the ulcer region and intact region were also increased as compared with that of the normal control region. 2) Changes in serotonin (5-HT) content as well as HA content were observed. 3) Norepinephrine content in the ulcer region was decreased as compared with the intact region at 2, 10, 80 and 180 days. 4) HDC activity in the ulcer region was decreased as compared with the intact region at 2, 10 and 40 days, and a lower level was maintained still at 180 days. 5) In the relapse and recurrence of gastric ulcer at 365 days, HA and 5-HT contents in the intact region and ulcer region were not different from those in healing rats, but the contents of these amines were higher at 180 days. The results suggest that the change of HA, 5-HT contents and HDC activity in the gastric mucosa may be one of the factors involved in the relapse and recurrence of chronic ulcers.View full abstractDownload PDF (4380K) -
Tsukasa KIRIMOTO, Kaori OHTANI, Hiroaki YAMADA, Shigeki FUJISAWA, Yuta ...1989 Volume 93 Issue 3 Pages 119-131
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSThe effects of LC-80, infused intravenously at a rate of 10 mg/kg/min for 30 min, on hemodynamics and myocardial metabolism were investigated in anesthetized open-chest dog preparations under a normal oxygen tension of arterial blood (PaO2) ranging from 100 to 120 mmHg or low PaO2 ranging from 40 to 50 mmHg. (1) Normal PaO2+High free fatty acidemia (HFFA) : HFFA was produced by the intravenous infusion of Intralipid at a rate of 0.1 ml/kg/min after the rapid intravenous injection of 500 U/kg of heparin. Under this experimental condition, no significant changes in hemodynamics and myocardial metabolism were observed in both the LC-80 treated group and control group. (2) Low PaO2+HFFA: Under this condition, there was no significant difference in hemodynamics between the LC-80 treated group and the control group, and the myocardial function in both groups tended to decrease. However, the increase in the coronary flow of the LC-80 treated group tended to be slight as compared with that of the control group. On the other hand, the decrease in the arterio-coronary venous difference of lactate was significantly less in the LC-80 treated group as compared to that in the control group. Furthermore, the reduction in myocardial redox potential (ΔEh) of the LC-80 treated group tended to be slight as compared with that of the control group. (3) Low PaO2+HFFA+stress load: The hemodynamic responses (heart rate, left ventricular pressure, max dP/dt and cardiac work) to isoproterenol-induced stress were slightly but not significantly better in the LC-80 treated group than in the control group. While myocardial lactate production and the reduction of ΔEh in both groups became more prominent under this experimental condition, their degrees were apparently less in the LC-80 treated group as compared to those in the control group. These results suggest that LC-80 may have an improving effect on the anaerobic myocardial metabolism under anaerobic conditions such as hypoxia or stress load.View full abstractDownload PDF (10654K) -
Susumu OKABE, Koji TAKEUCHI, Megumu OKADA, Yasuki KUMADAKI, Mika NAKAT ...1989 Volume 93 Issue 3 Pages 133-144
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSWe examined the antisecretory and antilesion activities of nizatidine in rats. Male SD or Donryu rats (200-260 g) were used under fasted or fed conditions. Nizatidine, given orally or parenterally (intraperitoneally, subcutaneously or intraduodenally) at 0.3 ?? 150 mg/kg, inhibited both basal (pylorus-ligation preparations) and histamine-stimulated gastric acid secretion (acute fistula preparations) in a dose-dependent manner. The potency of nizatidine was 2 to 8 times greater than cimetidine when the ED50 values (mg/kg or μ mole/kg) of each agent were compared. The antisecretory activity of nizatidine, given orally, persisted for more than 3.5 hr, but disappeared 6 hr later. Nizatidine, given orally or subcutaneously at 0.3 ?? 150 mg/kg, prevented development of gastric lesions induced by water immersion, pylorus ligation (Shay), histamine, aspirin, or indomethacin in a dose-dependent manner. Duodenal ulcers induced by mepirizole were also markedly prevented with nizatidine. The potency of nizatidine on stress lesions or duodenal ulcers was about 20 or 14 times greater than that of cimetidine, respectively. Nizatidine, given orally 3 times a day for 4 weeks, significantly (P<0.05) accelerated the healing of acetic acid-induced gastric ulcers which were delayed by prolonged treatment with indomethacin. These results suggest that nizatidine is a useful drug for the treatment of peptic ulcers in man.View full abstractDownload PDF (8715K) -
Akira IKEGAMI, Akemi MAEDA, Hideaki HARA, Akira YAMASHITA, Takayuki SU ...1989 Volume 93 Issue 3 Pages 145-154
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSThe effects of trazodone (KB-831) and its metabolites on the uptake, turnover and contents of monoamines in rats were studied in comparison with those of imipramine and mianserin. Trazodone exhibited a more potent inhibitory effect on the uptake of [3H] 5-hydroxytryptamine (5-HT) into brain synaptosomes than on the uptake of [3H]norepinephrine (NE). Trazodone at 10 ?? 30 mg/kg, p.o., also inhibited the p-chloramphetamine-induced depletion of 5-HT in rat brain, but not the 6-hydroxydopamine-induced NE depletion in rat heart. Trazodone was the most selective 5-HT uptake inhibitor among the drugs tested in vitro. Its metabolite, m-chlorophenyl-piperazine (m-CPP), inhibited 5-HT and NE uptake in vitro, but not in vivo. Trazodone (100 mg/kg) and imipramine (30 ?? 100 mg/kg) inhibited the depletion of NE induced by α-methyl-p-tyrosine, whereas mianserin (100 mg/kg) facilitated it. At l hr after a single administration of each drug, an increase in 5-HT content and a decrease in 5-hydroxyindole-3-acetic acid (5-HIAA) content were observed when 30 mg/kg trazodone was used. At 100 mg/kg, trazodone increased the levels of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and decreased the NE content. m-CPP (10 ?? 30 mg/kg) produced similar effects on monoamine contents to those of trazodone. Imipramine and mianserin had no effect on monoamine contents even at a dose of 100 mg/kg. After 3 weeks of successive administration, an increase in 5-HT and a decrease in .5-HIAA were induced by trazodone and m-CPP at 1 hr, but not at 17 hr, after the final administration. Imipramine decreased the contents of NE and 5-HIAA, and its effects lasted for 17 hr. These results suggest that trazodone is a selective 5-HT uptake inhibitor and that its neurochemical profile is different from those of imipramine and mianserin.View full abstractDownload PDF (7865K) -
Tsukasa KIRIMOTO, Yuko MORIKAWA, Hiroaki YAMADA, Shigeki FUJISAWA, Yut ...1989 Volume 93 Issue 3 Pages 155-169
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSThe cardiovascular effects of levocarnitine chloride (LC-80) were investigated in in vitro and in vivo experiments, and the following results were obtained: (1) In isolated rabbit cardiac muscle preparations, LC-80 at the high concentration of 10-2M had little influence on the artrial rate of spontaneously beating right atria, while it caused a gradual increase in the contractile tension of both spontaneously beating right atria and electrically driven papillary muscle that reached a maximum level after 10 min of administration and lasted for 20 ?? 30 min. However, the LC-80-induced positive inotropic effect may be negligible in whole animal experiments or clinical trials, since it was elicited only after the administration of LC-80 in an extremely large dose. Furthermore, LC-80 in a high concentration (10-2 M) had no influence on the isoproterenol-induced positive inotropic effect in electrically driven papillary muscles. (2) LC-80 in high concentrations of 10-3 ?? 10-2M did not affect the high K+-induced contraction in isolated canine left circumflex coronary artery and saphenous vein. (3) In anesthetized dogs, intraarterial injection of LC-80 in high doses of up to 10 mg did not change the blood flow of coronary, femoral, renal, mesenteric or vertebral arteries and on the adenosine-induced vasodilator action. (4) In anesthetized dogs, intravenous injection of LC-80 in doses of 100 ?? 300 mg/kg did not modify the blood pressure responses induced by norepinephrine, acetylcholine, carotide occlusion and vagal stimulation. These results suggest that the cardiovascular effects of LC-80 are extremely mild or negligible. Therefore, LC-80 may be a drug having a new pharmacological feature in its mechanism which enables it to exert a beneficial effect in the treatment of ischemic heart disease, being different from the commonly used antianginal drugs.View full abstractDownload PDF (10158K) -
Hisato KAKUSHI, Tsutomu SHIKE, Kiyohisa UCHIDA1989 Volume 93 Issue 3 Pages 171-178
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSThe newly synthesized compound S-145, (±) -5(Z)-7 (3-endo-phenylsulfonylamino [2.2.1] bicyclohept-2-exo-yl)heptenoic acid, inhibited arachidonic acid (AA)-, 9, 11-methanoepoxyPGH2 (U46619)-, collagen- and ADP-induced human platelet aggregation in vitro with IC50 values of 0.25, 0.34, 0.22, and 0.08 μM, respectively. The inhibiting potency of this compound to AA or U46619-induced platelet aggregation was about twice that of ONO-3708 and 1/7 ?? 1/14 that of SQ29, 548 in human platelets, about 7 times that of ONO-3708 and 1/3 ?? 1/7 that of SQ29, 548 in guinea pig platelets, and 250 ?? 800 times that of ONO-3708 and 1 ?? 7 times that of SQ29, 548 in rabbit platelets. When S-145 was administered orally to guinea pigs at the dose of 0.1 mg/kg, AA-induced platelet aggregation was completely inhibited at 30 and 60 min after the administration, but not at 3 and 6 hr. The minimum effective doses of S-145 (p.o.) to AA- and collagen-induced platelet aggregation at 60 min after the administration were 0.01 mg/kg and 0.03 mg/kg, respectively. The potency of S-145 (p.o.) to inhibit AA- and collagen-induced guinea pig platelet aggregation was 30 ?? 300 times that of ONO-3708 or SQ29, 548 and 300 ?? 1000 times that of aspirin. These results suggest that S-145 is a thromboxane A2 antagonist showing a potent inhibiting effect on platelet aggregation by oral administration.View full abstractDownload PDF (5413K) -
Masako GOTO, Hajime INOUE, Yoshiyuki SEYAMA, Saburo YAMASHITA, Osamu I ...1989 Volume 93 Issue 3 Pages 179-186
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSIn order to clarify the anti-hyperglycemic and anti-hyperlipidemic actions of traditional Chinese medicines, experiments were carried out with experimentally diabetic rats induced by cyproheptadine treatment. The following results were obtained: 1) Dai-saiko-to decreased the blood glucose level at 30, 60 and 120 min after glucose loading in the tolerance test; and the drug tended to increase serum insulin level and increased the ratio (glucose/insulin) at 120 min after the glucose loading. A significant decrease in serum total cholesterol was observed in the high fat diet-treated rats. 2) Hatimi-zio-gan also decreased the blood glucose level at 30 and 120 min after glucose loading. The drug did not lower the serum insulin, but rather increased the glucagon level at 120 min after the loading. The serum lipid level was not reduced by the drug. 3) Byakko-ka-ninzin-to also increased serum glucagon at 120 min, but no change of glucose and lipid in the sera under the above experimental conditions was observed. Such experimental results suggest that Dai-saiko-to might exert an effect that can improve the pathological conditions of diabetes mellitus.View full abstractDownload PDF (5033K) -
Hidehiko NAKAGAWA, Shigeru ARITA, Sawako KOBAYASHI, Yukihiro IKOMA, No ...1989 Volume 93 Issue 3 Pages 187-196
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSEffects of non-ionic contrast media on the central nervous system were compared in order to clarify any differences due to the side-chain structures among iopamidol, iotrolan, iocibidol, iohexol, iopromide, iosimide and metrizamide. The study included a primary screening test based on Irwin's method, antielectric convulsive tests using mice, measurement of the blood pressure using rats and electroencephalography using rats and rabbits. The general behavior of mice in the primary screening test revealed that tolerance to iopamidol, iotrolan and iocibidol was excellent; that to iopromide and iohexol was moderate; and that to iosimide and metrizamide was poor. Iosimide and iohexol suppressed the transient increase of blood pressure upon intravenous administration in the normal rats but not in the pithed rats. Electric stimulus increased the mortality of mice pretreated with iosimide and iohexol. Abnormal EEG with epileptic seizures, slow wave and/or flattening were observed with the administration of iopromide, iosimide or metrizamide as well as ionic contrast media. From these results, it was concluded that iopromide and metrizamide were not well tolerated in general behavior and EEG; iohexol, in general behavior, electroshock and blood pressure; and iosimide, in all experiments, while iopamidol, iotrolan and iocibidol were well tolerated. Therefore, small differences in their side-chain structures among these contrast media are considered to cause different effects on the central nervous system.View full abstractDownload PDF (6726K) -
Yoshihiro KIYOTA, Masaomi MIYAMOTO, Akinobu NAGAOKA1989 Volume 93 Issue 3 Pages 197-202
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSThe ameliorating effects of idebenone and indeloxazine hydrochloride on the impairment of memory and learning were studied in cerebral embolized rats. The embolized rats had impaired memory and learning ability in the radial maze task; these were demonstrated by a decrease in correct responses and an increase in total errors. In particular, the rats showed severe impairment of working memory, as shown by a marked increase in the numbers of re-entries into the arm that had been already visited. Idebenone (30 mg/kg, p.o.) exerted marked ameliorating effects on the impairment in the embolized rats: the drug significantly increased the correct responses and decreased the errors. Indeloxazine hydrochloride also improved the memory impairment in the embolized rats, as shown by a reduction of the errors. The ameliorating effects of these drugs may be due mainly to improvement of hypofunctions of the central nervous system. These results confirm that idebenone and indeloxazine hydrochloride may have ameliorating actions on impairment of memory and learning induced by brain hypofunction, and they suggest that the action of idebenone is more potent than that of indeloxazine hydrochloride.View full abstractDownload PDF (4008K)
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