巻号一覧
47 巻 (1988)
- 4 号 p. 333-
- 3 号 p. 209-
- 2 号 p. 107-
- 1 号 p. 1-
47 巻, 1 号
選択された号の論文の15件中1～15を表示しています
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Shintaro NISHIO, Hirotoshi MATSUURA, Noriko KANAI, Yuko FUKATSU, Tetsu ...1988 年 47 巻 1 号 p. 1-10
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーEffect of TRK-100, a stable PGI2 analog, on platelet function was tested in vitro and ex vivo. TRK-100 at the dose range of 0.5-300 nM inhibited platelet aggregation induced by arachidonic acid, adenosine 5'-diphosphate and collagen in several species including human platelets. The potency of TRK-100 was 1/2 to 1/5 that of PGI2. The effect was strong in human and cat platelets. In conscious rabbits and rats, oral TRK-100 at the dose range of 0.1-1 mg/kg inhibited ex vivo platelet aggregation up to 80% in the rat and 70% in the rabbit, and the effect lasted over 5 hr. However, in both species, the effect on blood pressure was minimal. In anesthetized rabbits, inhibition of platelet aggregation was the same level as in the conscious animal, but blood pressure depression was observed. Cyclic AMP levels of human platelets, 2 min after incubation, was elevated up to 2.4 μM/109 platelets by 100 ng/ml of PGI2 and 1.5 μM by 100 ng/ml of TRK-100. It was shown that TRK-100 has a potent antiplatelet effect both in vitro and ex vivo in many species through elevation of platelet cAMP. These results suggest that TRK-100 may be a potential oral antithrombotic drug.抄録全体を表示PDF形式でダウンロード (441K) -
Shigehiro OHDO, Shigeyuki NAKANO, Nobuya OGAWA1988 年 47 巻 1 号 p. 11-19
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーEffects of the time-of-day of drug administration on the pharmacokinetics electroshock seizure (ES) threshold and acute toxicity were investigated in mice with sodium valproate (VPA). ICR male mice, housed under a light-dark (12:12) cycle, were orally administered 600 mg/kg VPA for anticonvulsant effect studies and administered 1 500 mg/kg VPA for acute toxicity studies. A significant circadian rhythm was demonstrated for the ES threshold at 30 min after VPA administration, with the highest value in the light phase and the lowest in the dark phase, although no rhythm was shown in the nondrugged state. A significant circadian rhythm was also shown for plasma and brain VPA concentrations. This finding nicely corresponded to the circadian rhythm in the ES threshold. The positive relationship between the brain VPA concentration and the ES threshold was not different between the light phase and the dark phase. There was also a significant circadian rhythm in the acute toxicity induced by VPA, with the highest mortality in the light phase and the lowest in the dark phase. The results suggest the importance of time in the circadian stage at which VPA is administered in the experimental studies in mice and the significance of circadian rhythm in VPA kinetics in relation to the rhythm of ES threshold.抄録全体を表示PDF形式でダウンロード (539K) -
Haruo KOBAYASHI, Akira YUYAMA, Tetsuji OHKAWA, Toshihiko KAJITA1988 年 47 巻 1 号 p. 21-27
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーPropoxur, an anticholinesterase carbamate, was injected singly (10 mg/ kg, s.c.) or chronically (5 mg/kg/day, s.c., for 10 days) into mice. Animals were examined for effects on the cholinergic system in brain tissue and on behavior. Single injection caused an increase in brain acetylcholine (ACh) content at 10 and 60 min; and it caused decreases in acetylcholinesterase (AChE) activity at 10, 60 and 180 min, high-affinity choline uptake into synaptosomes at 10 and 60 min, and [3H]quinuclidinyl benzilate (QNB) binding at 10 min without causing any change in choline acetyltransferase (ChAT) activity. Open-field behavior and rotarod performance were depressed at 10 min and rectal temperature was decreased at 10, 60 and 120 min after a single injection. Chronic treatment caused decreases in high-affinity choline uptake and [3H]QNB binding 24 hr after the final injection without any changes in ACh content, AChE activity or ChAT activity. In behavioral tests conducted 10 min prior to daily administration, rotarod performance was slightly suppressed only during the period of injection. Although propoxur is considered to have effects similar to those of organophosphorus compounds, the changes observed in the present experiments seemed to be reversible.抄録全体を表示PDF形式でダウンロード (409K) -
Hiroaki SHIRAHASE, Yukiko SUZUKI, Seimei OSUMI, Nobuharu KAKEYA, Kazuy ...1988 年 47 巻 1 号 p. 29-34
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーAggregation, serotonin release and malondialdehyde (MDA) production via cyclooxygenase and thromboxane A2 synthetase were investigated in rabbit platelets. Trimetazidine dihydrochloride (TMZ) attenuated the collagen-induced aggregation more strongly than the arachidonic acid (AA)-, thromboxane A2 agonist (U-46619)-, Ca2+-ionophore (A-23187)- and ADP-induced aggregation: IC50 values were 1.0±0.1, 4.4±0.3, 4.3±0.4, 4.1±0.7 and 3.3±0.2 mM, respectively. TMZ decreased dose-dependently the serotonin release induced by collagen and A-23187, but did not decrease that induced by AA. TMZ also decreased the MDA production induced by collagen and A-23187 (IC50: 0.3±0.03 and 1.0±0.1 mM, respectively), but did not decrease the production induced by AA. Furthermore, TMZ decreased dose-dependently the MDA production induced by exogenous phospholipase A2. On the other hand, indomethacin (10 μM) attenuated the aggregations induced by collagen and AA, but not by the other agents, and decreased the serotonin release and the MDA production induced by collagen, A-23187 and AA. The present results suggest that TMZ may inhibit the process preceding the cyclooxygenase pathway in the AA cascade, and subsequently may attenuate the aggregation and the serotonin release via thromboxane A2 production from endogenous AA.抄録全体を表示PDF形式でダウンロード (335K) -
Akira KARASAWA, Kazuhiro KUBO1988 年 47 巻 1 号 p. 35-44
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーThe newly-developed 1, 4-dihydropyridine derivative KW-3049 was investigated for calcium antagonistic effects in isolated canine coronary arteries. KW-3049 relaxed the arteries contracted by KCl-depolarization with an IC50 of 7.4×10-9 M, while the IC50 of nifedipine, verapamil and diltiazem were 9.1×10-9 M, 1.7×10-7 M and 3.1×10-7 M, respectively. Comparison with negative inotropic activities examined in electrically-driven canine papillary muscles indicated that KW-3049 was more selective for vasorelaxing versus negative inotropic activities than nifedipine, verapamil and diltiazem. KW-3049 inhibited 45Ca-uptake induced by depolarization without affecting 45Ca-uptake in polarized arteries. Inhibitory effects of KW-3049 at 10-9 and 10-8 M on depolarization-induced contractions of arteries exhibited no recovery for up to 4 hr after washout of the tissues, whereas those of nifedipine, nitrendipine, verapamil and diltiazem at vasoinhibitory concentrations disappeared within 1 to 4 hr after washout.抄録全体を表示PDF形式でダウンロード (565K) -
Satoshi YAMAMOTO, Itsumi KIYOTO, Eriko AIZU, Nobuyuki SASAKAWA, Toshio ...1988 年 47 巻 1 号 p. 45-49
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーIt has been reported that CD-1 and SENCAR mice are susceptible and C57BL/6 mice are resistant to skin tumor promotion caused by phorbol esters. Specific binding of a phorbol ester to its epidermal receptor site, epidermal protein kinase C activity, and ornithine decarboxylase (ODC) induction in epidermis were compared between tumor promotion-susceptible and -resistant strains of mice. Specific binding of[3H]12-O-tetradecanoylphorbol-13-acetate (TPA) to the particulate fraction of the epidermis of C57BL/6 mice gave a similar dissociation constant (Kd) and a maximal number of binding sites (Bmax) to those of CD-1 mice. Protein kinase C activity of the epidermal 105, 000×g supernatant was not significantly different between C57BL/6 and CD-1 mice. Protein kinase C activity of the 105, 000×g pellet, however, was significantly higher in C57BL/6 mice than in CD-1 mice. A topical application of TPA to the skin caused epidermal ODC induction in all of these strains of mice. At any doses of TPA, TPA-induced epidermal ODC activity of C57BL/6 mice was always higher than those of SENCAR and CD-1 mice. Maximal induction of epidermal ODC by TPA was also highest in C57BL/6 mice among these three strains of mice. These results indicate that the mechanism of the difference in susceptibility of C57BL/6, CD-1 and SENCAR mice to the tumor-promoting action of TPA resides in a step distal to or other than the protein kinase C activation and ODC induction.抄録全体を表示PDF形式でダウンロード (292K) -
Isao FUKUCHI, Kazutaka KAWASHIMA, Yuzo MATSUOKA, Ryuichi ISHIDA1988 年 47 巻 1 号 p. 51-61
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーMafoprazine, a phenylpiperazine derivative, was neurochemically investigated in rats to determine its action mechanism. The rank order of affinity of mafoprazine for neuronal receptors was D2≥α1>S2>α2 >> D1>β>mACh. The affinity of mafoprazine for D2 receptors (Ki=10.7 nM) was 2 times higher than that of azaperone, and 6 and 16 times lower than those of chlorpromazine and haloperidol, respectively, whereas the D2 receptor selectivity [D1/D2 (Ki value ratio)] of mafoprazine was 10, 9 and 2 times higher than those of chlorpromazine, azaperone and haloperidol, respectively. The affinity of mafoprazine for α2 receptors in terms of the ratio of the Ki values for D2 and α2 receptors (D2/α2) was 345, 26 and 3 times higher than those of haloperidol, chlorpromazine and azaperone, respectively. Mafoprazine slightly showed the inhibitory effect on dopamine-stimulated adenylate cyclase (IC50=52300 nM), and it had almost no affinity for β and mACh receptors. Mafoprazine significantly increased dopamine metabolites in the corpus striatum and nucleus accumbens, although to lesser extents as compared with azaperone and chlorpromazine. These results suggest that mafoprazine probably manifests its antipsychotic action mainly through D2 receptor blocking activity and α-adrenergic activity (α1 receptor blocking activity and α2 receptor stimulating activity).抄録全体を表示PDF形式でダウンロード (559K) -
Anutosh Ranjan SAHA, Koichi UENO, Shigeru OHMORI, Takashi IGARASHI, Ha ...1988 年 47 巻 1 号 p. 63-69
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーHeptaminol AMP amidate (HAA), a newly developed derivative of 5'-AMP, was found to potentiate the in vitro primary humoral immune response against T cell-dependent antigen, sheep red blood cells, when HAA was present in the early phase of spleen cell culture. Such a potentiating effect was not found against T cell-independent antigens such as lipopolysaccharide (LPS), trinitrophenylated (TNP)-LPS and TNP-Ficoll. The pattern of HAA-mediated immunopotentiation was similar to that of dibutyryl cyclic AMP. When HAA was added to the culture simultaneously with theophylline and imidazole, the immunopotentiating effect of HAA was further augmented and suppressed, respectively. The present results suggested that HAA-mediated immunopotentiation might be in some way related to the intracellular level of cyclic nucleotides in the early phase of culture.抄録全体を表示PDF形式でダウンロード (439K) -
Norio HIMORI, Tsutomu ISHIMORI1988 年 47 巻 1 号 p. 71-80
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーI.v. propranolol (Prop) produced sustained pressor responses in rats but not in dogs under urethane anesthesia. In the dogs there was a progressive reduction in systolic blood pressure (SBP) in accordance with a significant heart rate (HR) reduction. Even at the i.v. dose (5 mg/kg) where vasoconstrictor response to i.v. norepinephrine (NE) is changed to the vasodilator one in rats, phenoxybenzamine could not completely suppress the NE-induced vasoconstriction in dogs. In pithed dogs, unlike pithed rats, i.v. Prop augmented neither sympathetic nerve stimulation- nor i.v. epinephrine (Epi)-induced pressor responses. Urethane anesthesia brought much higher concentrations in plasma Epi and NE in the dog than in the rat. In comparison with their respective values under the conscious state, SBP and HR of the dog were higher and those of the rat were lower under urethane anesthesia. As in urethane-anesthetized dogs, j.v. Prop elicited remarkable HR reduction accompanied by progressive hypotension in coronary-ligated rats with high sympathetic activity. Thus the reason for the absence of pressor response to β-receptor blockage in the dog may be due to less functional significance of β2-adrenoceptor-mediated vasodilation in determining the peripheral vascular tone; and also, the possibility that there may be the involvement of an inverse influence of urethane on the cardiovascular regulatory system in terms of enhancing sympathetic nervous activity in the dog and a decreasing one in the rat can not be ruled out.抄録全体を表示PDF形式でダウンロード (627K) -
Tomonori KUROKAWA, Toshio DAN'URA, Atsushi YAMASHITA, Yasutomo UNE, Sa ...1988 年 47 巻 1 号 p. 81-86
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーThe effect of diazepam on the adenylate cyclase system was studied in rat synaptosomal membranes. Micromolar concentrations of diazepam inhibited the cyclase activities in the presence or absence of guanylyl-5'-1midodiphosphate (GppNHp). The inhibitory effect of diazepam was greater on the cyclase activity in the presence of GppNHp than on that in the basal state. This effect of diazepam was not antagonized by Rol5-1788, an antagonist of a high affinity benzodiazepine receptor in the central nervous system. Furthermore, micromolar concentrations of Rol5-1788 had no inhibitory effect on cyclase activities in the presence or absence of GppNHp. In addition, the bromide ion enhanced the inhibition by diazepam of the cyclase activity in the presence of GppN Hp, but not the basal activity, although the bromide ion had no effect on both activities in the absence of diazepam. On the other hand, the pretreatment of synaptosomal membranes with GppNHp increased the KD value for [3H]diazepam binding from 98 μM to 198 μM. These data led us to conclude that diazepam inhibits rat brain adenylate cyclase through the effects on both a low affinity benzodiazepine receptor coupled with the inhibitory GTP-binding regulatory protein (G1) and the catalytic protein.抄録全体を表示PDF形式でダウンロード (357K) -
Renato GAGGI, Rosaria DE IASIO1988 年 47 巻 1 号 p. 87-90
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーThe intracerebroventricular administration of salmon calcitonin (sCT) to rats induced a dose-dependent increase in the number of head twitches and potentiated such a response elicited by L-5-hydroxytryptophan (L-5-HTP). Subcutaneously administered sCT was ineffective “per se” but could again potentiate the head twitch response elicited by L-5-HTP. Since these data suggest a stimulation of the brain serotonergic pathways, the obtained results support the hypothesis that some central actions of sCT may involve activation of serotonergic systems in the rat brain.抄録全体を表示PDF形式でダウンロード (190K) -
Tokio NAKANE, Shigetoshi CHIBA1988 年 47 巻 1 号 p. 91-94
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーWe studied the mechanisms of pindolol-induced vasoconstrictions in isolated and perfused monkey coronary arteries. Phentolamine marginally reduced the vasoconstrictions, but bunazosin and DG 5128 did not. Diltiazem and methysergide significantly inhibited them, but atropine, diphenhydramine and cimetidine did not. Diltiazem significantly suppressed KCl-induced vasoconstrictions, but methysergide did not. These results suggest that pindolol-induced vasoconstrictions of monkey coronary arteries are mediated, at least partly, through 5-hydroxytryptamine receptors, but not through α-adrenoceptors, and that these vasoconstrictions appear to be associated with an increase of Ca2+ entry into the smooth muscle cell.抄録全体を表示PDF形式でダウンロード (240K) -
Toshitsugu OGURA, Ichiro WATANABE, Tomoaki SAITO, Satoshi SAITO, Yukio ...1988 年 47 巻 1 号 p. 95-98
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーEffects of OKY-046, a selective thromboxane synthetase inhibitor, on ischemia-induced ventricular arrhythmias were investigated in anesthetized dogs. OKY-046 (30 mg/kg, intravenously) decreased ventricular arrhythmias significantly both during 30 min of coronary artery ligation and subsequent reperfusion, which corresponded with a significant reduction of thromboxane concentration, suggesting that thromboxane released during ligation is an important factor in the development of ventricular arrhythmias. Inhibition of thromboxane synthesis with OKY-046 might be useful for the prevention of ischemia-induced ventricular arrhythmias.抄録全体を表示PDF形式でダウンロード (205K) -
Katsuo KAMATA, Akemi SAKAMOTO, Yutaka KASUYA1988 年 47 巻 1 号 p. 99-102
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーThe changes in sensitivity of the rat stomach fundus to acetylcholine (ACh), norepinephrine (NE), isoproterenol (ISO) and to vasoactive intestinal peptide (VIP) were examined in control rats and in streptozotocin (STZ) induced diabetic rats. The dose-response curves for drugs were constructed 8 weeks after treatment with STZ. The dose-response curve for ACh in diabetic rats was shifted to the left as compared to the control curve, whereas the dose-response curves for NE, ISO and VIP were shifted to the right. These results suggest that functional changes in the autonomic nervous systems of the rat stomach fundus may occur in STZ-induced diabetic rats.抄録全体を表示PDF形式でダウンロード (161K) -
Jian Ying WANG, Koji TAKEUCHI, Susumu OKABE1988 年 47 巻 1 号 p. 103-105
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーOral administration of 60% ethanol in 150 mM HCl(HCl·ethanol) to rats produced gastric mucosal lesions within 1 hr. PGE2 given s.c. at 0.1 to 3 mg/kg 0.5 hr before HCl·ethanol significantly prevented the lesion formation. The protection afforded with 3 mg/kg of PGE2 persisted for 6 or 12 hr after administration. PGE2 given s.c. at 3 mg/kg significantly inhibited gastric secretion in pylorusligated and intact rats, but the action disappeared 6 hr later.抄録全体を表示PDF形式でダウンロード (176K)
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