The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
47 巻, 4 号
選択された号の論文の12件中1~12を表示しています
  • Shuichi HARA, Satoshi YANAGIHARA, Kazunori SATOH, Shigeo MORIOKA
    1988 年 47 巻 4 号 p. 333-340
    発行日: 1988年
    公開日: 2006/08/25
    ジャーナル フリー
    Effects of systemically administered γ-aminobutyric acid (GABA) on indomethacin-induced gastric ulceration were studied in rats. Orally administered GABA significantly exacerbated the ulceration in a dose-dependent manner, although GABA per se had no ulcerogenic activity. The exacerbation was restored by GABA receptor antagonists, bicuculline methiodide, picrotoxin and pentylenetetrazol. Pretreatment with atropine sulfate antagonized the exacerbating effect of GABA on indomethacin-induced ulceration. 3-Amino-1-propanesulfonic acid, but not glycine, taurine or β-alanine, mimicked the effect of GABA on the ulceration, which was inhibited by picrotoxin. Muscimol and (-)-baclofen could not potentiate the ulceration. However, sodium pentobarbital and diazepam caused synergistic exacerbation of the ulcer when combined with GABA. Since it is known that systemically administered GABA can not penetrate into the brain, these results suggest that systemically administered GABA may stimulate the cholinergic transmission mediating the activation of peripheral GABA receptors, resulting in the exacerbation of indomethacin-induced ulceration.
  • Jun-ichi KAWAGOE, Nobuyoshi SUNAGANE, Tsutomu URUNO, Kazuhiko KUBOTA
    1988 年 47 巻 4 号 p. 341-347
    発行日: 1988年
    公開日: 2006/08/25
    ジャーナル フリー
    Effects of D 600, papaverine and KCN on sustained contracture induced by 20 mM KCI in a Na+-free sucrose- or Tris-substituted solution were investigated in the taenia coil of guinea pigs. D 600 (10-5 M) and papaverine (10-4 M), added after 40 min incubation in the 20 mM KCI sucrose solution, relaxed the muscle by 88.2±8.0% (mean±S.E., n=4) and 78.8±6.3% (n=4), respectively. In contrast to this, KCN (10-3 M) relaxed the muscle by 11.0±4.7% (n=4) after a 20 min incubation in the sucrose solution. The concentration-relaxation curves for these relaxants were slightly shifted to the right in the Na+-free 20 mM KCI Tris solution. The cellular Na+ content of the taenia coil was greatly reduced by exposure to the sucrose or Tris solution, while the Ca2+ contents in both solutions were gradually increased with the exposure time. When a glucose-free solution was applied 60 min after the KCI-induced sustained contracture, gradual relaxation in the normal solution was observed. This relaxation was completely inhibited in the Na+-free sucrose solution. These results suggest that the relaxing activities of the different inhibitors are changed to different degrees by the replacement of Na+ with sucrose in the guinea-pig taenia coil and that sustained KCI-contracture in a Na+-free sucrose solution may be less energy-dependent as compared with that in a Na+-free Tris medium. These results also indicate the inability to directly correlate the changes in the Ca2+ and Na+ contents with the greatly reduced activities of the relaxants in a Na+-free sucrose solution.
  • Taeko HATA, Atsufumi KAWABATA, Tomitaro KITA, Eiji ITOH, Yoshitaka NIS ...
    1988 年 47 巻 4 号 p. 349-356
    発行日: 1988年
    公開日: 2006/08/25
    ジャーナル フリー
    In order to hematologically characterize SART-stressed (repeated cold-stressed) animals, which are regarded as model animals of clinical dysautonomia, general hematological analyses were performed in mice subjected to various types of stress. SART-stressed mice showed significant increases in erythrocyte count, hemoglobin, hematocrit and specific gravity of whole blood, no change in leukocyte count and a marked decrease in platelet count. Among the above changes, the decreased platelet count was particularly characteristic of SART-stressed mice. Splenectomy failed to inhibit the SART stress-induced thrombocytopenia. Bone marrow megakaryocyte counts increased following the stress. The bleeding time of SART-stressed mice was more than double that of normal mice. Consecutive administrations of Neurotropin®, a sedative analgesic, completely blocked the alterations in platelet count, megakaryocyte count and bleeding time in SART-stressed mice without producing any effect in unstressed mice. From the present results, it is suggested that SART-stressed mice may be characterized by thrombocytopenia, which is not attributable to enhanced function of the spleen or suppressed platelet production in the bone marrow. Moreover, Neurotropin appears to be effective for moderating SART stress.
  • Minoru MATSUURA, Seiji SATOH, Fumihiko KOBAYASHI, Takashi MATSUBARA, K ...
    1988 年 47 巻 4 号 p. 357-365
    発行日: 1988年
    公開日: 2006/08/25
    ジャーナル フリー
    Feeding of a vitamin K-deficient diet caused the development of hypoprothrombinemic changes in rats such as prolongation of prothrombin time (PT) and activated partial thromboplastin time (APTT), decreases in plasma prothrombin and clotting factor VII levels, and an increase in the descarboxyprothrombin (PIVKA) level in both plasma and liver. Successive administrations of latamoxef (LMOX) to the vitamin K-deficient rats resulted in the further enhancement of these changes. After the development of hypoprothrombinemia with LMOX, a single subcutaneous injection of vitamin K1 normalized most of these abnormalities in blood coagulation parameters within 6 hr. When vitamin K was given at 200 μg/kg, PT, APTT and the plasma PIVKA level showed normal values for at least 8 days even when the animals were fed a vitamin K-deficient diet and treated with LMOX during the recovery period. The amount of vitamin K required to maintain most of the blood coagulation parameters in the normal range was about 3 μg/kg/day. The plasma level of vitamin K was higher than 0.3-0.5 ng/ml when the blood coagulation parameters were maintained in the normal range.
  • Kayoko MOROI, Katsuo TAKASHI, Tetsuro KUGA
    1988 年 47 巻 4 号 p. 367-378
    発行日: 1988年
    公開日: 2006/08/25
    ジャーナル フリー
    Harmine (HA) induces a jumping behavior in rats when the central dopaminergic function has been activated. Possible involvement of the GABAergic systems and the benzodiazepine receptors (BZA-R) in the jumping behavior induced by HA and apomorphine (APO) was investigated. Pretreatment with GABAergic agonists, muscimol (0.05-0.2 mg/kg) and diazepam (0.2-1.0 mg/kg), and antagonists, picrotoxin (0.1-0.5 mg/kg) and bicuculline (0.1-0.5 mg/kg), suppressed the jumping behavior in a dose-dependent manner in rats treated with HA (10 mg/ kg) and APO (2 mg/kg). After treatment with 2, 5 or 10 mg/kg of HA in combination with 2 mg/kg of APO, a decrease in 3H-diazepam binding to the brain regional membranes was observed in the corpus striatum (CS) in a dose-dependent manner, but not in the other brain regions. The decrease in the 3H-diazepam binding to the CS membranes was proportional to the increase in the HA levels in the CS, and the HA levels were correlated with the intensity of jumping behavior. Pretreatment with Ro 15-1788, an antagonist of BZA-R, suppressed the jumping behavior induced by HA and APO. These results indicated the involvement of the GABAergic systems in the jumping behavior and suggested that HA induced the jumping behavior partly as a result of interacting with the BZA-R.
  • Masao HISADOME, Yuka KIMURA, Kiyoteru IKEGAMI, Michio TERASAWA
    1988 年 47 巻 4 号 p. 379-385
    発行日: 1988年
    公開日: 2006/08/25
    ジャーナル フリー
    L-Cysteine ethylester hydrochloride (ethylcysteine; 30 mg/kg, p.o.) increased the number of la-positive cells (antigen presenting cells) in spleen adherent cells (SAC) and that of Lyt 1.2-positive cells (helper T cells), but not that of Lyt 2.2-positive cells (suppressor T cells) of C57BL/6 mice immunized with sheep red blood cells. The production of hemolytic plaque forming cells (HPFC) in spleens of syngeneic recipient mice was enhanced by the transfer of SAC or spleen lymphocytes of the donor mice pretreated with ethylcysteine. This drug augmented phagocytosis of yeast particles by peritoneal macrophages of ICR mice at concentrations of 1-100 μM. In ex vivo experiments, this drug (30 mg/kg, p.o.) augmented the phagocytosis of yeast particles by mouse macrophages and showed a tendency to increase the macrophage number in the peritoneal cavity. Ethylcysteine (30 mg/kg, p.o.) significantly accelerated the decrease of viable E. coli number in the liver of normal mice 2 and 48 hr after challenge. Furthermore, this drug at the same dose restored the suppression of the decrease of E. coli number in the blood and liver of mice treated with cyclophosphamide (200 mg/kg, i.p.). These results suggest that ethylcysteine augments the functions of macrophages in vitro and ex vivo, and these enhancing effects may lead to the enhancement of host resistance to infections in compromised hosts.
  • Junko NAKASONE, Takayuki KATO, Katsuhiko NOGUCHI, Fumio NAGAMINE, Mata ...
    1988 年 47 巻 4 号 p. 387-395
    発行日: 1988年
    公開日: 2006/08/25
    ジャーナル フリー
    The effects of atenolol and another three beta-adrenoceptor blocking agents on norepinephrine (NE)-induced cardiac responses were examined in isolated and perfused rat hearts following a Langendorff method. Bolus injection of atenolol did not show significant inhibitory effects on NE-induced increases in myocardial contractile force (MCF) and heart rate. Bolus injections of metoprolol and timolol were also ineffective for inhibiting NE-responses. However, both bolus injection and infusion of propranolol or infusion of atenolol, metoprolol and timolol all significantly inhibited NE-responses. On sustained increase in MCF induced by infusion of NE, the inhibitory effect of atenolol was transient, while that of propranolol was continuous. From these results, it is concluded that atenolol displays a different time course of action on NE-induced cardiac responses by bolus injection or infusion because of its pharmacological properties, which may be due to its low lipophilicity.
  • Koji TAKEUCHI, Hideyuki NISHIWAKI, Susumu OKABE
    1988 年 47 巻 4 号 p. 397-408
    発行日: 1988年
    公開日: 2006/08/25
    ジャーナル フリー
    Effects of topical application of omeprazole on transmucosal potential difference (PD), luminal pH and histamine-stimulated acid secretion were examined in anesthetized rat stomachs, and they were compared with those of systemic administration. Omeprazole was suspended in 1% CMC with NaHCO3 (pH 9.0) or dissolved in 0.1 N HCl (pH 1.0). Both omeprazole (30 mg/kg, pH 9.0) and cimetidine (100 mg/kg), given i.d., increased the pH and inhibited acid secretion induced by histamine (8 mg/kg/hr, i.v.), while basal gastric PD was markedly elevated only by the former. Similar responses in PD, pH and acid output were obtained dose-dependently after brief exposure of the stomach (10 min) to omeprazole (0.3-30 mg/kg), even in acidic conditions, but the effects of acidified omeprazole disappeared depending upon the latency period in 0.1 N HCl; there was no effect when applied at more than 30 min after dissolution. Of interest, subsequent exposure of the stomach to a mercaptane compound (cysteine, 100 mg/kg) for 30 min significantly reversed the antisecretory effect of omeprazole (both i.d. and i.g.) but not of cimetidine. These results suggest that omeprazole has a local antisecretory action even in acidic stomachs, probably through an inhibition of the H+/K+ ATPase activity, and the increase of PD caused by omeprazole may be a characteristic phenomenon seen after the blockade of H+/K+ ATPase, but is not associated with acid inhibition itself.
  • Takayuki DOI, Seiji KUZUNA, Masahiko FUJINO
    1988 年 47 巻 4 号 p. 409-415
    発行日: 1988年
    公開日: 2006/08/25
    ジャーナル フリー
    The analgesic action of the enkephalin analog EK-399 (Tyr-D-Met(O)-Gly-EtPhe-NHNHCOCH3·AcOH) and the subtypes of the opiate receptors mediating the action were studied. The analgesic effect of subcutaneously injected EK-399 was ten times as potent as that of morphine in the rat tail flick test. EK-399 had a longer latency time and duration time than morphine. The analgesic action of EK-399 injected into the rat spinal subarachnoid space was about 800 (1800 in molar ratio) times as potent as that of morphine in the hot plate test. EK-399 had high affinities for both μ and δ opiate receptors in the rat brain receptor binding assay. The apparent pA2 values with naloxone were 7.65 for morphine and 5.98 for EK-399 in the rat tail flick test; the difference was significant. A cross tolerance between EK-399 and morphine was examined in the rat tail flick test. Although morphine tolerant rats showed no tolerance to EK-399, EK-399 tolerant rats showed a clear tolerance to morphine. These results indicate that EK-399 has a potent and long lasting analgesic effect via opiate receptors in rats. In addition to μ-receptors, δ-receptors may be involved in its analgesic mechanism.
  • Hiroaki NUMATA, Toyokazu HIRANUMA, Tetsuo OKA
    1988 年 47 巻 4 号 p. 417-423
    発行日: 1988年
    公開日: 2006/08/25
    ジャーナル フリー
    Inactivation of dynorphin-(1-8) in three in vitro isolated preparations, guinea-pig ileum, mouse vas deferens and rabbit vas deferens, was estimated by employing the relatively specific inhibitors of enkephalin-hydrolyzing enzymes. All three enzyme inhibitors, amastatin, captopril and phosphoramidon, significantly enhanced the inhibitory potency of dynorphin-(1-8) in the three isolated preparations. The magnitude of the enhancement of the dynorphin potency by captopril was significantly higher than that by either amastatin or phosphoramidon in guinea-pig ileum; that by amastatin was significantly higher than that by either captopril or phosphoramidon in rabbit vas deferens; and that by amastatin was similar to that by captopril, but significantly higher than that by phosphoramidon in mouse vas deferens. The Ke values of three antagonists, naloxone, Mr 2266 and ICI 154129, against dynorphin-(1-8) in the presence of the three peptidase inhibitors indicated that dynorphin-(1-8) acted on kappa receptors in guinea-pig ileum and on both kappa and delta receptors in mouse vas deferens. Since amastatin, captopril and phosphoramidon produced the naloxone-reversible inhibition of contractions of guinea-pig ileum in the presence of dynorphin-(1-8), all three dynorphin-inactivating enzymes were indicated to be located very close to kappa receptors.
  • Tsutomu SUZUKI, Kokichi OTANI, Yoko KOIKE, Miwa MISAWA
    1988 年 47 巻 4 号 p. 425-431
    発行日: 1988年
    公開日: 2006/08/25
    ジャーナル フリー
    Preferences for morphine and codeine in two inbred strains of rats, Lewis and Fischer 344 (F344), were systematically investigated using the drug-admixed food (DAF) procedure. Rats were allowed access to food only between 10:00 a.m.-4:00 p.m., but allowed free access to water. The rats were allowed to choose either DAF (0.5 mg/g) or normal food on the first day and then were allowed access only to DAF on the second and third days. After this schedule was repeated 10 times, they were again allowed to choose either DAF or normal food for a successive 8 days. In both strains, preferences for morphine and codeine rapidly increased; the preferences in Lewis rats were significantly higher than those in F344 rats during the daily choice trials. In the range of 0.25 to 1 mg/g for the DAF concentration, there was a negative correlation between the preference and concentration in Lewis and F344 rats, except in the codeine group of F344 rats. When a test dose (60 mg/kg and 30 mg/kg, s.c., in Lewis and F344 rats, respectively) of morphine or codeine was given at 30 min before the beginning of the choice trial, Lewis rats, but not F344 rats, showed a significantly lower preference for the respective drug. The above results indicate that genotype is an important determinant of the degree of preferences for morphine and codeine.
  • Haruo YOSHII, Takao MATSUOKA, Yoshiyuki KURIMOTO, Seishi SUEHIRO
    1988 年 47 巻 4 号 p. 433-435
    発行日: 1988年
    公開日: 2006/08/25
    ジャーナル フリー
    Effect of Neurotropin on the delayed type hypersensitivity (DTH) response to sheep red blood cells was examined in mice. Neurotropin suppressed the high DTH responses in ddY and BALB/c mice, while it enhanced the low DTH response in C57BL/6 mice when administered after sensitization. In addition, Neurotropin exerted a suppressive effect on the enhanced DTH response by cyclophosphamide pretreatment in C57BL/6 mice, but had a restorative effect on the suppressed DTH response in ddY mice loaded with restraint stress.
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