The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
53 巻, 4 号
選択された号の論文の18件中1~18を表示しています
  • Kentaro AKIYAMA, Keitaro HASHIMOTO
    1990 年 53 巻 4 号 p. 419-426
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    Triggered activity due to delayed afterdepolarization has been postulated to be one of the generation mechanisms of some arrhythmias, especially that due to digitalis toxicity. The present experiment demonstrates an in vivo canine model of ventricular arrhythmias that were triggered by ventricular stimulation during administration of low doses of ouabain. Ventricular ectopic beats could be induced by stimulation before the occurrence of spontaneous ventricular arrhythmia, and the coupling interval of the first ectopic beat was shortened as the stimulation rate increased. Verapamil (0.2 mg/kg, i.v.) was ineffective in suppressing the occurrence of the triggered ventricular ectopic beats, but lidocaine (1 and 3 mg/kg, i.v.) and disopyramide (0.3 and 1 mg/kg, i.v.) were effective in suppressing these digitalisinduced triggered ventricular ectopic beats in a dose-dependent fashion.
  • Hitoshi KONTANI, Mikiko NAKAGAWA, Satoshi TAKENO, Takeshi SAKAI
    1990 年 53 巻 4 号 p. 427-433
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    We studied the effects of drugs used for treatment of bladder dysfunction in conscious rats with intact pelvic nerves and also in rats at one or two weeks after nerve decentralization on the left side. Bladder contraction accompanying micturition was continuously induced by infusion of solution at a constant rate. When the effects of oxybutynin (3 mg/kg, i.p.) and terodiline (3 and 10 mg/kg, i.p.) on the cystometrogram were studied for about 2 hr, these drugs shortened and then prolonged the micturition interval (MI), but atropine (1 and 5 mg/kg, i.p.), butylscopolamine (20 mg/kg, i.p.) and nifedipine (3 mg/kg, i.p.) exhibited only a shortening effect on the MI. After injection of oxybutynin (10 mg/kg, i.p.), solution dribbled from the urethra for about 30 min. Terodiline (3 mg/kg) caused ischuria in the rats one week after resection of the left pelvic nerve, but not in the rats two weeks after surgery. Physostigmine (0.3 mg/kg, i.p.) improved micturition in the rats one week after surgery, but the effect was not evident in the rats with intact pelvic nerves. It was found that the drugs used for treating failure to store or expel urine exhibited a beneficial effect on micturition in rats with intact pelvic nerves and also in rats one week after nerve decentralization, respectively.
  • Rei YOSHIDA, Kazuo ICHIHARA, Yasushi ABIKO
    1990 年 53 巻 4 号 p. 435-441
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    Effects of a selective α1-adrenergic blocking agent, bunazosin, on myocardial energy metabolism in the ischemic heart were studied. Ischemia was induced by ligating the left anterior descending coronary artery of the dog heart. Bunazosin was injected intravenously either 5 or 20 min before coronary artery ligation. Hearts were removed 3 min after coronary ligation and used for determination of the levels of cardiac tissue metabolites. Ischemia decreased the levels of ATP, creatine phosphate, glycogen and glucose, and increased the levels of ADP, AMP, hexose monophosphates and lactate. The energy charge potential (ECP) calculated was decreased by ischemia. Pretreatment with bunazosin inhibited the decrease in ATP and the increase in AMP caused by ischemia, resulting in the high value of ECP in the ischemic myocardium. Bunazosin also prevented the changes in carbohydrate metabolism caused by ischemia. It is concluded that bunazosin may reduce the influence of ischemia on the myocardium.
  • Nobuyuki NISHIDA
    1990 年 53 巻 4 号 p. 443-450
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    The physical dependence potential of Tyr-D-Met(O)-Gly-EtPhe-NHNH000H3·AcOH (EK-399), a novel enkephalin analog with a potent analgesic effect, was assessed in rats. The animals were given EK-399 (0.008, 0.032, 0.125, or 0.5 mg/kg), morphine (0.125, 0.5, or 2 mg/kg), pethidine (2 or 8 mg/kg), or pentazocine (2 or 8 mg/kg) every hour through an implanted intravenous cannula. After 3 days of treatment, precipitated withdrawal tests were conducted: naloxone (5 mg/kg) was administered subcutaneously. Rats treated with morphine showed withdrawal signs such as hyperirritability, salivation, diarrhea, and weight loss. Rats treated with pethidine, pentazocine, or EK-399 showed similar signs, but they were less evident than those in morphine-treated rats. In abrupt withdrawal tests after 7 days of treatment, rats treated with morphine, pethidine, or pentazocine showed weight loss, whereas rats treated with EK-399 showed little or no weight loss. In substitution tests, EK-399 suppressed the withdrawal signs in morphine-dependent rats, and vice versa. These results show that EK-399 has a morphine-like physical dependence potential that is weaker than that of morphine, pethidine, or pentazocine in rats.
  • Michio YAMAMURA, Kiyoshi KINOSHITA, Hiroyuki NAKAGAWA, Takashi TANAKA, ...
    1990 年 53 巻 4 号 p. 451-461
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    Effects of orally administered TA-0910, a new thyrotropin-releasing hormone (TRH) analog, on the central nervous system (CNS) were investigated and compared with those of TRH. TA-0910 shortened the duration of pentobarbital-induced sleep and antagonized reserpine-induced hypothermia at 0.3 mg/kg or more in mice. TA-0910 enhanced the spontaneous motor activity at the higher dose of 30 mg/kg in mice. The drug also activated acute spontaneous EEGs in rabbits at 1 mg/kg. TRH produced these effects at about 100 times higher doses than TA-0910. In antagonizing pentobarbital-induced sleep, the dose ratios of i.v. versus p.o. of TA-0910 and TRH were about 1/10 and 1/100, respectively. The duration of the antagonistic action of TA-0910 on pentobarbital-induced sleep in mice was about 8 times longer than that of TRH when administered orally as well as intraveneously. These potent and long-acting TA-0910 effects on the CNS are discussed in connection with its biotransformation.
  • Kikuo MASUDA, Takaaki NAKAMURA, Kyoichi SHIMOMURA
    1990 年 53 巻 4 号 p. 463-472
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    FK973 (11-acetyl-8-carbamoyloxymethyl-4-formyl-l4-oxa-1, 11 -diazatetracyclo[7.4.1.O2, 7O10, 12]tetradeca-2, 4, 6-trien-6, 9-diyl diacetate), a new substituted dihydrobenzoxazine, has potent cytotoxic and antitumor effects on murine and human tumors in vivo and in vitro, and forms interstrand DNA-DNA and DNA-protein cross-links after being activated in the cytoplasm. In this study, the mechanism(s) by which FK973 is activated in the cytoplasm of in vitro cultured murine L1210 leukemia cells were studied using compounds that affect monoamine oxidase. When the cells were incubated with an antitumor drug and the compounds, tranylcypromine, benzylamine, phenylethylamine and tyramine of the many compounds tested reduced the cytotoxicity of FK973, but not that of mitomycin C or cisplatin. These compounds also suppressed the formation of interstrand DNA-DNA crosslinks with FK973 in the cells, but did not suppress cross-links with mitomycin C or cisplatin. The incorporation of 14C-FK973 into the cells was not affected by these compounds. The results suggest that FK973 is activated by some drug-metabolic system(s) in the cytoplasm to form interstrand DNA-DNA cross-links, and induces cytotoxicity against the cells. This activation of FK973 in the cytoplasm is discussed in connection with the drug-metabolic system(s) in relation to the structures of the compounds.
  • Sumio SHIMA, Nobu AKAMATU
    1990 年 53 巻 4 号 p. 473-478
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    The effects of an adenosine analog, N6-phenyl-isopropyl-adenosine (PIA), on the glucagon-stimulated adenylate cyclase activity in rat hepatic membranes were studied. Adenosine at high concentrations (>10 μM) has been reported exclusively to inhibit the adenylate cyclase via intracellular P-sites of the hepatic membrane. The stimulation by glucagon of the enzyme was attenuated by nanomolar concentrations of PIA in the presence of low concentrations (<1.0 μM) of GTP, indicating the effect of the guanine nucleotide inhibitory system (Ni). This inhibition by PIA required the presence of sodium chloride and was antagonized with isobutyl methylxanthine, an antagonist for the extracellular R-site receptors. The inhibitory effects of PIA disappeared and reversed into a stimulatory phase with increasing concentrations of GTP, suggesting the presence of a stimulatory (Ns) and an inhibitory (Ni) guanine nucleotide system of the enzyme in the action of the adenosine. PIA concentrations over a micromolar were observed to stimulate the enzyme activity in a GTP-dependent manner, indicating the presence of the stimulatory receptor (A2 or Ra) coupled to the Ns. These results suggest that receptors for adenosine of the inhibitory type (A1 or Ri) and the stimulatory type (A2 or Ra) are present on the rat hepatic membrane, showing multiple controls of the adenylate cyclase system, depending on the cellular concentrations of GTP and/or sodium chloride.
  • Tadatoshi HASHIMOTO, Naohisa FUKUDA
    1990 年 53 巻 4 号 p. 479-486
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    Spinal cord injuries in rats were experimentally produced by compressing the cord at the eleventh thoracic vertebral level for 60 minutes with stainless steel screws (2 mm in diameter and 2.8 mm in length). The main neurologic signs produced by cord compression were motor as well as sensory deficits and urinary incontinence. Rats with a neurologic score, based on both motor and sensory deficits, of 1 (complete paraplegia but responsive to tail pinching) 24 hours after injury were used to study the relative effect of subcutaneous treatment with TRH once or twice daily for 7 consecutive days on the time course of recovery after spinal cord injury and the dose-dependency of this effect. Once daily (5, 15, or 45 mg/kg/day) or twice daily (2.5, 7.5, or 22.5 mg/kg × 2/day) treatment with TRH starting 24 hours after injury improved the neurological signs and reduced the incidence of urinary incontinence, dose-dependently. The minimum effective doses for once and twice daily treatments were 45 mg/kg/day and 7.5 mg/kg × 2/day. These results indicate that the neurologic recovery-accelerating effect of TRH administered 24 hours after cord injury for 7 days is dose-dependent and that a twice daily dosage schedule tends to produce better improvement in the neurologic state than a once daily schedule dose.
  • Masakatsu TAKAHASHI, Toshihiko SENDA, Shogo TOKUYAMA, Hiroshi KANETO
    1990 年 53 巻 4 号 p. 487-494
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    The analgesic effect induced by exposure to psychological stress, using a communication box (psychological stress-induced analgesia, PSY-SIA), was completely antagonized by 10 min pretreatment with 0.5, 1 and 2 mg/kg of nor-binaltorphimine and with 0.5 and 1 mg/kg of Mr2266, selective κ-opioid receptor antagonists, in the tail pinch method. Neither footshock (FS)- nor forced swimming (SW)-SIA was affected by these antagonists. The selective δ-opioid receptor antagonist naltrindole, at doses up to 20 mg/kg, had no appreciable effect on PSY-SIA. Daily morphine treatment, 10 mg/kg, s.c., resulted in tolerance to the analgesic effect, and concurrent exposure to PSY-stress suppressed the development of morphine tolerance. The substitution of treatment with U-50, 488H for PSY-stress still resulted in analgesia on the initial day; and likewise, the suppression by U-50, 488H of the development of morphine tolerance was replicated by PSY-stress. Pretreatment with nor-binaltorphimine antagonized the suppressive effect of PSY-stress on the development of morphine tolerance without affecting the analgesic effect of morphine per se. These results provide further evidence that PSY-SIA involves the mediation by κ-opioid receptor mechanisms.
  • Francesco SQUADRITO, Anna L. BUEMI, Rosa STURNIOLO, Michele BUEMI, Fra ...
    1990 年 53 巻 4 号 p. 495-498
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    Intracerebrove ntricuIar (i.c.v.) injection of magnesium sulphate (MgSO4: 2.5, 5 and 10 μmol in 5 μl) decreased blood pressure and heart rate in both anesthetized normotensive (WKY) and hypertensive rats (SHR). The effects were greater in WKY than in SHR. Moreover, a pretreatment with hexamethonium (2 mg/kg, i.v.) significantly blunted the hypotensive and bradycardic effects induced by i.c.v. injection of 10 μmol of MgSO4 in both WKY and SHR. Our data suggest that MgSO4 produces hypotensive and bradycardic effects when injected i.c.v. in both WKY and SHR.
  • Tetsuo SHIMIZU
    1990 年 53 巻 4 号 p. 499-501
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    Solcoseryl®(SOL) and Cardiocrome®(CAR) produced decreases in the partial oxygen pressure of platelet suspensions, indicating the acceleration of platelet oxygen consumption. However, the peak response to CAR was much faster than that to SOL. Application of 1 ml of SOL to 20 ml of platelet suspension stored for 1 day produced increases of 1 nmol ATP per min per 109 platelets. The same increases in oxygen consumption appeared after 3 or 5 day-storage.
  • Satoru TANAKA, Shin-ichiro ASHIDA, Akira AKASHI
    1990 年 53 巻 4 号 p. 502-505
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    The effects of antihypertensive drugs on ischemic cerebral damage were investigated using the bilateral carotid artery occlusion (BCAO) model in SHR. Oral budralazine and nifedipine, at doses that increased cerebral blood flow (CBF) in SHR in our previous study (Tanaka, S. et al., Folia Pharmacol. Japon. 87, 1986), significantly improved cerebral energy failure after the BCAO, but prazosin which does not increase CBF had no effect on the energy failure. These results suggest that the amelioration by these antihypertensive drugs of the energy failure after the BCAO results from its CBF-increasing effects in SHR.
  • Miwa MISAWA, Yoshinori TAKAHASHI, Junzo KAMEI, Tomokazu HOSOKAWA, Saiz ...
    1990 年 53 巻 4 号 p. 506-509
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    Afferent cervical vagal electrical stimulation caused a reflex tracheal constriction. Atropine changed the tracheal constriction into a tracheal dilatation that was almost inhibited by propranolol. In the hypertonic trachea with 5-hydroxytryptamine, a reflex dilatation following a constriction was observed by afferent vagal stimulation. The reflex dilatation was inhibited about 50% by propranolol and was abolished by hexamethonium. These results suggest that the adrenergic and nonadrenergic inhibitory innervations may mediate the reflex tracheal dilatation, especially in a hypertonic tracheal condition.
  • Fumitoshi ASAI, Takeshi OSHIMA
    1990 年 53 巻 4 号 p. 510-514
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    Erythrocytes in anemic rats with adjuvant arthritis (AA) were less deformable compared with normal rats. Swelling of the spleen was noticed in anemic rats with AA. The treatment of anemic rats with recombinant human erythropoietin (r-HuEPO; 30 and 100 U/kg, i.v., for 5 days) resulted in a normalization of both the anemia and erythrocyte deformability. It is suggested that erythrocytes with reduced deformability may be sequestered by endothelial slits of the spleen, which may play a causative role in the anemia in rats with AA.
  • Takehiko ITAYA, Hisakuni HASHIMOTO, Ryuichi SATOH, Toshihiko UEMATSU, ...
    1990 年 53 巻 4 号 p. 515-518
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    The alteration in adrenoceptors in the hypertrophied right ventricle of the rats with myocardial infarction (MI) was examined. The density of alpha-1- adrenoceptors increased in four and twelve week old MI rats but not in one week old MI rats. The beta-adrenoceptors did not significantly change. It is probable that the increased density of alpha-adrenoceptors may be one of the causes for the increased responsivenesss to the alpha-adrenergic agonist in the hypertrophied cardiac muscles of MI rats.
  • Masaaki HIROHASHI, Kiyoshi TAMURA, Akira AKASHI
    1990 年 53 巻 4 号 p. 519-520
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    Midaglizole (3 and 30 mg/kg, i.v.) increased blood pressure in pithed rats. The pressor response was not inhibited by intravenous prazosin (0.3 mg/ kg), yohimbine (1 mg/kg), ketanserin (1 mg/kg) or diphenhydramine (5 mg/kg). Diltiazem (1 mg/kg) antagonized the hypertension. Idazoxan (10 mg/kg) also increased blood pressure, and the pressor response was inhibited by prazosin, but not by yohimbine. These results suggest that the vascular effect of midaglizole is due to a mechanism different from that of idazoxan.
  • Ikunobu MURAMATSU, Shigeru KIGOSHI, Yasuo ODA
    1990 年 53 巻 4 号 p. 521-523
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    In the presence of prazosin and propranolol, electrical transmural stimulation of isolated dog mesenteric artery produced a sympathetic purinergic contraction, which was followed by a relaxation in PGF-contracted arteries. Such purinergic responses were mimicked by brief exposure to α, β-methylene ATP (α, β-Me ATP) and were completely inhibited after desensitization of P2x-purinergic receptors. However, exogenous ATP predominantly evoked a relaxation in PGF-contracted artery. These results suggest that the sympathetic purinergic response may be caused by a P2x-purinergic receptor-selective mechanism or substance, rather than ATP.
  • Issei TAKAYANAGI, Hiroshi OHTSUKI
    1990 年 53 巻 4 号 p. 525-528
    発行日: 1990年
    公開日: 2006/07/11
    ジャーナル フリー
    Pilocarpine, which activates propylbenzilylcholine mustard (PrBCM)-sensitive cholinoceptors, and carbachol, which activates PrBCM-resistant ones, induced an increase in cytosolic Ca2+ concentration ([Ca2+]i) and tension development in a concentration dependent manner in isolated longitudinal muscle of guinea pig ileum. A positive correlation between [Ca2+]i and tension development due to both of the agonists was noted. The slope of regression line between two values for pilocarpine was steeper than that for carbachol, suggesting that pilocarine induced greater tension for a given increase in [Ca2+]i than did carbachol. Thus an activation of PrBCM-sensitive cholinoceptors might enhance the Ca2+-sensitivity of the contractile elements.
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