The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 66, Issue 1
Displaying 1-23 of 23 articles from this issue
  • Yasukuni Hirouchi, Hideo Naganuma, Yukinori Kawahara, Ryuzo Okada, Aki ...
    1994 Volume 66 Issue 1 Pages 1-6
    Published: 1994
    Released on J-STAGE: April 10, 2006
    JOURNAL FREE ACCESS
    The preventive effect of betamipron (N-benzoyl-3-propionic acid: BP) on the renal uptake and nephrotoxicity of carbapenems (panipenem and imipenem) was studied in rabbits. Panipenem, a new carbapenem antibiotic, induced nephrotoxicity at a dose of 200 mg/kg, i.v., but this was less severe than that caused by a single dose of imipenem or cephaloridine. Along with the significant reduction of nephrotoxicity, the uptake of these carbapenems in the renal cortex was remarkably inhibited by simultaneous treatment with BP (200 mg/kg, i.v.). These results suggest that BP reduces the nephrotoxicity of carbapenems through inhibiting the active transport of carbapenems in the renal cortex. Because of the low toxicity of BP (LD50 in the rat, more than 3, 000 mg/kg, i.v.), it was concluded that BP might be a good candidate for reducing the nephrotoxicity induced by panipenem or imipenem.
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  • Tetsuo Ohashi, Akihiko Watanabe, Toshiaki Nishigaki, Hiroshi Azuma
    1994 Volume 66 Issue 1 Pages 7-16
    Published: 1994
    Released on J-STAGE: April 10, 2006
    JOURNAL FREE ACCESS
    When rat mast cells sensitized by IgE antibody were exposed to antigen, transmission electron microscopy revealed alteration of the granules, cavity formation by fusion of the perigranular membrane and granule release by the fusion of the cavity membrane with the mast cell membrane. Scanning electron microscopy disclosed the extrusion of smooth and round bodies from pores formed on the cell surface. These changes were accompanied by the release of histamine. The inhibition of this degranulation by a novel anti-allergic agent, 6-(1-pyrrolidinyl)-N-(1H-tetrazol-5-yl)-2-pyrazinecarboxamide (PTPC), was evaluated quantitatively as an inhibition of the granule alteration and cavity formation. At a concentration of 100 nM, PTPC inhibited the granule alteration and cavity formation as well as histamine release. In the same concentration, PTPC significantly increased the cyclic AMP content in the mast cells. These results suggest that the inhibition of the morphological changes in mast cells by PTPC might be due to the increased cyclic AMP caused by the agent and plays an important role in the suppression of chemical mediators release.
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  • Mamoru Saito, Suguru Suzuki, Yoshiki Yui, Chuichi Kawai
    1994 Volume 66 Issue 1 Pages 17-23
    Published: 1994
    Released on J-STAGE: April 10, 2006
    JOURNAL FREE ACCESS
    In a canine copper coil-induced coronary thrombosis model, the differences in frequency of reperfusion arrhythmias (premature ventricular complexes: PVC) and mortality rate after thrombolysis by intravenous bolus injection of a novel modified tissue-type plasminogen activator (t-PA), E6010, and by continuous intravenous infusion of native t-PA or urokinase were evaluated. Rapid coronary occlusion and reperfusion were produced with a balloon catheter in another group of dogs, and the findings were compared with those in the thrombolysis groups. Reperfusion occurred gradually after the administration of E6010, but was significantly more rapid after administration of native t-PA and urokinase (P<0.05). PVC were observed more frequently in native t-PA, urokinase and balloon occlusion-reperfusion groups than in the E6010 group. The mortality rate due to ventricular fibrillation was 0.0% in the E6010 group, 50.0% in the native t-PA and balloon occlusion-reperfusion groups, and 33.3% in the urokinase group. These results suggest that the more gradual reperfusion of the coronary artery at an earlier period after drug administration led to the lower frequency of reperfusion arrhythmias and low mortality rate in the E6010 group than in the native t-PA, urokinase and balloon occlusion-reperfusion groups.
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  • Masahiro Tsuchimoto, Yoshiaki Azuma, Osamu Higuchi, Izuki Sugimoto, No ...
    1994 Volume 66 Issue 1 Pages 25-33
    Published: 1994
    Released on J-STAGE: April 10, 2006
    JOURNAL FREE ACCESS
    The bisphosphonates, which are carbon-substituted pyrophosphates, have been studied extensively both in vivo and in vitro to elucidate their effects on bone tissues and cells. However, because these agents were shown to have a potent inhibitory effect on bone resorption, the majority of studies have focused on only this aspect of bone metabolism. There appears to be less information regarding the direct effect of bisphosphonates on bone formation, so thus we undertook experiments to investigate the effects of bisphosphonates, especially alendronate, on the mineralization and matrix protein synthesis of human osteoblastic cells in vitro. The data show that the bisphosphonates, alendronate, etidronate and pamidronate, suppressed 1, 25-dihydroxycholecalciferol (1, 25(OH)2D3)-stimulated mineralization of human osteoblastic cells at high concentrations, while relatively lower concentrations of alendronate and etidronate potentiated mineralization of the cells in the presence of 1, 25(OH)2D3. The potentiation of mineralization with alendronate was accompanied by increased synthesis of bone matrix proteins, osteocalcin and collagen, and the mRNA of pro α(I) collagen. These findings show that in addition to their well-known effects on bone resorption, bisphosphonates have significant and direct effects on osteogenesis in osteoblasts in vitro. The actual mechanism remains to be further investigated.
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  • Takayuki Kato, Katsuhiko Noguchi, Matao Sakanashi
    1994 Volume 66 Issue 1 Pages 35-46
    Published: 1994
    Released on J-STAGE: April 10, 2006
    JOURNAL FREE ACCESS
    The antihypertensive effect of 7-O-ethylfangchinoline (TJN-220) was analyzed in an experimental model of hypertensive rats under the conscious condition. Single oral administration of TJN-220 (25 and 50 mg/kg) produced a progressive and long-lasting fall of mean blood pressure in spontaneously hypertensive rats (SHRs), deoxycorticosterone acetate (DOCA)-salt hypertensive rats and renal hypertensive rats until 72 hr after the drug administration, but affected neither the heart rate in these hypertensive rats nor the hemodynamic parameters in normotensive rats. In SHRs implanted with a telemetry transmitter, TJN-220 (50 mg/kg, p.o.) produced falls of systolic and diastolic blood pressures and diminished the difference in blood pressure between the dark period and the light period for 3 days, particularly by suppressing the increasing phase of blood pressure during the dark period without influencing heart rate or locomotor activity. On the other hand, nicardipine (10 mg/kg, p.o.) produced a transient fall of blood pressure associated with a tachycardia during the light period on the first day alone. Clonidine (0.3 mg/kg, p.o.) diminished the increasing phases of blood pressure and heart rate during the dark period on the first day alone. Thus, the antihypertensive action of TJN-220 was much longer than those of nicardipine and clonidine. The present results suggest that TJN-220 may have potential for use as a beneficial antihypertensive drug.
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  • Kazumi Hayashi, Tadashi Nagamatsu, Mikio Ito, Tomohisa Hattori, Yoshio ...
    1994 Volume 66 Issue 1 Pages 47-52
    Published: 1994
    Released on J-STAGE: April 10, 2006
    JOURNAL FREE ACCESS
    We investigated the effect of acteoside in comparison with that of cyclosporin A on leukocyte accumulation in the glomeruli of rats with crescentic-type anti-glomerular basement membrane (GBM) nephritis. Acteoside given p.o. at a dose of 30 mg/kg once a day for 15 consecutive days after treatment with anti-GBM serum markedly suppressed the urinary protein as well as glomerular histological changes. Acteoside given p.o. for 5 or 15 consecutive days markedly suppressed the accumulation of total leukocytes, ED-1-positive cells (monocytes/macrophages), CD4-positive cells, CD8-positive cells, interleukin-2-receptor-positive cells (activated T cells) and la-positive cells in the glomeruli. These effects of cyclosporin A (20 mg/kg/day, p.o.) were also as potent as those of acteoside (30 mg/kg/day, p.o.). Cyclosporin A also strongly suppressed the elevation of plasma antibody level against rabbit γ-globulin. However, in this dose, acteoside did not significantly suppress the antibody formation. It can be concluded from these results that acteoside may exert its antinephritic action by suppressing the accumulation of leukocytes in the glomeruli.
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  • Kiyofumi Yamada, Tetsuo Hayashi, Takaaki Hasegawa, Seiichi Ishihara, T ...
    1994 Volume 66 Issue 1 Pages 53-58
    Published: 1994
    Released on J-STAGE: April 10, 2006
    JOURNAL FREE ACCESS
    We investigated the effects of the long-term administration of Kamikihito (KKT) on the specific binding of [3H]muscimol and [3H]flunitrazepam in the brains of young and aged rats using in vitro quantitative autoradiography. Specific [3H]muscimol binding in aged rats was decreased in all brain regions examined compared with that in young rats, whereas [3H]flunitrazepam binding did not change in any of the brain regions. Scatchard analysis revealed that the maximal number of [3H]muscimol binding sites in the cortex and thalamus was significantly decreased in aged rats compared with young rats, while its affinity remained unchanged. Long-term administration of KKT in young rats had no effect on either [3H]muscimol or [3H]-flunitrazepam binding. In contrast, the same treatment in aged rats produced a significant increase in [3H]-flunitrazepam binding to the cortex, caudate/putamen and accumbens, and it tended to decrease the [3H]-muscimol binding. These results suggest that the selective reduction of specific [3H]muscimol binding in the brain may be responsible, at least in part, for anxiety-related behavior in aged rats. Furthermore, it appears that the significant increase in specific [3H]flunitrazepam binding produced in the brains of aged rats by the long-term administration of KKT may be responsible for the anxiolytic effects of this agent.
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  • Noriaki Maeda, Nobuya Matsuoka, Isamu Yamaguchi
    1994 Volume 66 Issue 1 Pages 59-66
    Published: 1994
    Released on J-STAGE: April 10, 2006
    JOURNAL FREE ACCESS
    The neural mechanisms underlying the penile erection induced by serotonergic, cholinergic and dopaminergic stimulants were comparatively investigated. Fenfluramine (0.1-10 mg/kg, i.p.), pilocarpine (0.032-3.2 mg/kg) and apomorphine (0.01-1 mg/kg) induced penile erection in rats with bellshaped dose-response curves. The penile erection induced by fenfluramine (1 mg/kg) was dose-dependently antagonized by pindolol (0.1-3.2 mg/kg), a 5-HT1 antagonist, or scopolamine (0.032-1 mg/kg), a muscarinic antagonist, but not by sulpiride (1-32 mg/kg), a dopaminergic antagonist. The penile erection induced by pilocarpine (0.32 mg/kg) was countered by pindolol or scopolamine but not by sulpiride, while that induced by apomorphine (0.032 mg/kg) was countered by all three antagonists. Septo-hippocampal cholinergic deafferentations by medial septum lesioning or fimbria-fornix transection also significantly attenuated the penile erection induced by fenfluramine or apomorphine, but scarcely affected that induced by pilocarpine. Raphe lesion by injections of 5, 7-dihydroxytryptamine, a serotonergic neurotoxin, into the median and dorsal-raphe nuclei significantly attenuated the penile erections induced by fenfluramine and apomorphine but not that by pilocarpine. These results suggest that a neuronal link between the dopaminergic, serotonergic and cholinergic systems plays a crucial role in the expression of penile erection; dopaminergic stimulation causes an activation of the raphe serotonergic neurons which in turn enhances the septo-hippocampal cholinergic pathway and results in expression of penile erection.
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  • Hiroko Togashi, Machiko Matsumoto, Mitsuhiro Yoshioka, Mitsugu Hirokam ...
    1994 Volume 66 Issue 1 Pages 67-74
    Published: 1994
    Released on J-STAGE: April 10, 2006
    JOURNAL FREE ACCESS
    Acetylcholine (ACh) and choline (Ch) levels in rat cerebrospinal fluid (CSF) were determined by in vivo microdialysis (CSF microdialysis) in both halothane-anesthetized and freely-moving rats. The Ch/ACh ratio in CSF perfused with Ringer''s solution (30 μl/30 min) containing 10-5 M physostigmine, a centrally active cholinesterase inhibitor, was significantly lower than that in unprocessed CSF due to significantly higher ACh levels in the former. The successive measurement on the 2nd and 7th day after the guide cannula implantation demonstrated the feasibility of the CSF microdialysis method for repetitive monitoring of CSF ACh and Ch levels in freely moving rats without extensive tissue damage. Intraperitoneal administration of physostigmine caused an increase in CSF ACh levels, whereas administration of neostigmine, which cannot penetrate into the blood brain barrier, did not. Furthermore, a centrally active acetylcholinergic M1-receptor agonist, AF102B, produced an increase in CSF ACh and Ch levels. Thus, the present study demonstrates that CSF microdialysis is a useful method for evaluating overall central cholinergic activity and investigating the pharmacological effects of various drugs that act via the central cholinergic system.
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  • Ikuko Kimura, Mitsuhiro Makino, Yusaku Takamura, Md. Amirul Islam, Mas ...
    1994 Volume 66 Issue 1 Pages 75-80
    Published: 1994
    Released on J-STAGE: April 10, 2006
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    Aconitine and higenamine are the components of aconite root. We investigated the cardiac effects of these compounds on murine right and left atria and the interaction of higenamine with aconitine on the rate of spontaneously beating right atria. Higenamine increased the rate (EC50=38 nM) and the force of contraction (EC50=97 nM), the maximal responses being comparable with those of isoproterenol. The positive chronotropic effect of higenamine was antagonized by propranolol (30-300 nM) and practolol (10 nM 3 μM), but not by butoxamine (1 μM), indicating that it was a β1-adrenoceptor-mediated action. The positive chronotropic effect of higenamine was not changed by pretreatment with reserpine (4 mg/kg, i.p., 4 hr). Aconitine (0.16-0.25 μM) induced tachyarrhythmia in right atria was attenuated by quinidine (1 μM), atropine (8.6 μM) and AF-DX 116 (8.6 μM), suggesting that aconitine activates sodium channels and muscarinic receptors. Higenamine (2.5 nM) and dobutamine (1 nM) did not cause chronotropic effects by themselves, but enhanced the aconitine-induced tachyarrhythmia. These results indicate that higenamine is a β1-adrenoceptor full agonist in murine atria and that the aconitine-induced tachyarrhythmia is augmented by the β1-adrenergic action of higenamine.
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  • Hideaki Kusaka, Hiroko Nomura, Akira Karasawa
    1994 Volume 66 Issue 1 Pages 81-86
    Published: 1994
    Released on J-STAGE: April 10, 2006
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    Effects of benidipine on urine volume, excretion of electrolytes and renal hemodynamics were investigated in anesthetized spontaneously hypertensive rats (SHR). Benidipine at 3 and 10 μg/kg (i.v.) significantly increased urine volume, sodium (Na) and potassium (K) excretion with no change of creatinine clearance (CCRE). The increase in K excretion was relatively slight when compared with that in Na excretion. In another series of experiments, the tubular sites of action of benidipine were determined by the lithium clearance (CLi) technique and the stop-flow method. Benidipine at 3 μg/kg (i.v.) increased CLi, decreased creatinine concentration and increased Na concentration in the stop-flow urine from the distal nephron. These results suggest that benidipine produces diuresis and natriuresis by the inhibition of water and Na reabsorption at both the proximal tubule and the distal nephron. Benidipine increased p-aminohippuric acid clearance, but not CCRE, at doses of 3 and 10 μg/kg (i.v.), suggesting that benidipine dilates the glomerular efferent arteriole as well as the afferent arteriole. It is, therefore, expected that benidipine does not cause intraglomerular hypertension and has a beneficial effect in progressive renal disease.
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  • Tooru Abe, Takeshi Omata, Kenji Yoshida, Toshihiro Matsumura, Yugo Ike ...
    1994 Volume 66 Issue 1 Pages 87-94
    Published: 1994
    Released on J-STAGE: April 10, 2006
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    The antihistaminic effect of 2-[2-[4-(diphenylmethyl)-1-piperadinyl]ethoxy] benzoic acid maleate (ZCR-2060), a newly synthesized antiallergic agent, was investigated in both in vitro and in vivo studies. ZCR-2060 clearly antagonized histamine-induced contraction of isolated guinea pig ileum and trachea. In contrast, carbachol-, BaCl2 and 5-hydroxytryptamine-induced contractions of isolated guinea pig ileum were slightly inhibited by higher concentrations of ZCR-2060. 3H-Mepyramine specific binding to membranes from guinea pig lung and brain were markedly inhibited by ZCR-2060 in a concentration-dependent fashion. In the in vitro studies, the antihistaminic effect of ZCR-2060 was greater than those of cetirizine and terfenadine, but was less than that of ketotifen. In the in vivo studies, ZCR-2060 significantly inhibited the histamine-induced cutaneous reaction in rats, when administered orally 1 hr before the histamine injection. Moreover, ZCR-2060 has a long-lasting antihistaminic effect. In the in vivo studies, the antihistaminic effect of ZCR-2060 was found to be greater than that of cetirizine and terfenadine, and it was the same as that of ketotifen. Thiopental-induced sleep and spontaneous ambulatory activity in mice, however, were unaffected by ZCR-2060 at higher doses. These results indicate that ZCR-2060 has a potent, selective and long acting histamine H1-receptor antagonistic action without causing any unwanted CNS side effect.
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  • Tooru Abe, Takeshi Omata, Kenji Yoshida, Yoshihide Segawa, Kazuo Matsu ...
    1994 Volume 66 Issue 1 Pages 95-103
    Published: 1994
    Released on J-STAGE: April 10, 2006
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    The antiallergic action of 2-[2-[4-(diphenylmethyl)-1-piperadinyl]ethoxy] benzoic acid maleate (ZCR-2060) was investigated on allergic cutaneous reactions and nasal vascular permeability in mice and rats. ZCR-2060 markedly inhibited immediate allergic cutaneous reactions, including passive cutaneous anaphylaxis (PCA) in rats and mice; histamine-, compound 48/80- and calcium ionophore A 23187-induced cutaneous reactions in rats; and biphasic skin reactions mediated by monoclonal IgE antibody and epicutaneous challenge with antigen in mice, but did not affect 5-hydroxytryptamine-induced cutaneous reaction in rats. The antigen-induced nasal vascular permeability increase in actively and passively sensitized rats and histamine-induced nasal vascular permeability increase in rats (allergic rhinitis model) were clearly inhibited in a dose-dependent fashion by ZCR-2060. Moreover, ZCR-2060 significantly inhibited antigen-induced anaphylactic histamine release from rat peritoneal mast cells and carrageenin-induced paw edema in rats. These results suggest that ZCR-2060 has antiallergic effects on allergic cutaneous reactions and experimental rhinitis, probably due to histamine H1-receptor blockage and the inhibition of histamine release.
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  • Yasuhiro Tsukimi, Susumu Okabe
    1994 Volume 66 Issue 1 Pages 105-114
    Published: 1994
    Released on J-STAGE: April 10, 2006
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    Unilateral vagotomy causes atrophy of the denervated fundic mucosa in rat stomachs. We examined whether or not unilateral vagotomy delays healing of gastric ulcers induced on the denervated mucosa. Kissing ulcers were induced in the fundus of rat stomachs by intraluminal application of an acetic acid solution. Anterior unilateral vagotomy was performed subdiaphragmatically at the time of ulceration. The healing of gastric ulcers induced on the denervated side was significantly enhanced, whereas that on the vagally intact side was not affected. In unilaterally denervated animals, the total gastric acid secretion (both basal and 2-deoxy-D-glucose stimulated) was inhibited, and the pH around the ulcers was increased only in the anterior side. Repeatedly administered histamine failed to affect the enhanced ulcer healing in unilaterally denervated animals. Gastric emptying and mucosal cell proliferation stimulated by food or pentagastrin were unaffected. Serum gastrin significantly increased 19 days after vagotomy. Gastric relaxation on refeeding was inhibited on the denervated side, but this inhibition of relaxation was reversed by hexamethonium treatment. A liquid diet significantly enhanced the healing of ulcers on both the denervated and vagally intact sides. The mechanism by which unilateral vagotomy accelerates the healing of ulcers on the denervated side appears to relate to the inhibition of both gastric acid secretion and gastric relaxation.
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  • Shin Takayama, Yasuyuki Furukawa, Makoto Murakami, Shigetoshi Chiba
    1994 Volume 66 Issue 1 Pages 115-122
    Published: 1994
    Released on J-STAGE: April 10, 2006
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    We investigated whether pinacidil, a K+ATP channel opener like acetylcholine and adenosine, attenuated the positive chronotropic and inotropic responses to norepinephrine in isolated, blood-perfused dog atrial and ventricular preparations. Pinacidil (0.01-0.3 μmol) decreased atrial and ventricular contractile force to a much greater extent than sinus rate in a dose-related manner. Pinacidil dose-dependently attenuated increases in atrial and ventricular forces induced by norepinephrine but not increases in sinus rate. Pinacidil similarly attenuated the positive atrial and ventricular inotropic responses to Bay k 8644 and CaCl2. The pinacidil doses producing a fifty percent decrease (ED50) of the atrial and ventricular contractile force were not significantly different from the respective pinacidil doses producing a fifty percent inhibition (ID50) of the positive inotropic responses to norepinephrine, Bay k 8644 and CaCl2. Ouabain (5 and 15 nmol) did not affect the decreases in atrial and ventricular contractile force in response to pinacidil. These results suggest that the K+ATP-channel activator pinacidil, unlike acetylcholine or adenosine, functionally attenuates increases in ventricular and atrial contractile force in the responses to norepinephrine and other cardiotonics due to shortening of the action potential duration induced by K+ATP-channel activation in the dog heart.
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  • Yoko Aniya, Ai Daido
    1994 Volume 66 Issue 1 Pages 123-130
    Published: 1994
    Released on J-STAGE: April 10, 2006
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    The activation of microsomal glutathione S-transferase in oxidative stress was investigated by perfusing isolated rat liver with 1 mM tert-butyl hydroperoxide (t-BuOOH). When the isolated liver was perfused with t-BuOOH for 7 min and 10 min, microsomal, but not cytosolic, glutathione S-transferase activity was increased 1.3-fold and 1.7-fold, respectively, with a concomitant decrease in glutathione content. A dimer protein of microsomal glutathione S-transferase was also detected in the t-BuOOH-perfused liver. The increased microsomal glutathione S-transferase activity after perfusion with t-BuOOH was reversed by dithiothreitol, and the dimer protein of the transferase was also abolished. When the rats were pretreated with the antioxidant α-tocopherol or the iron chelator deferoxamine, the increases in microsomal glutathione S-transferase activity and lipid peroxidation caused by t-BuOOH perfusion of the isolated liver was prevented. Furthermore, the activation of microsomal GSH S-transferase by t-BuOOH in vitro was also inhibited by incubation of microsomes with α-tocopherol or deferoxamine. Thus it was confirmed that liver microsomal glutathione S-transferase is activated in the oxidative stress caused by t-BuOOH via thiol oxidation of the enzyme.
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  • Tsutomu Suzuki, Michiharu Yoshiike, Hirokazu Mizoguchi, Junzo Kamei, M ...
    1994 Volume 66 Issue 1 Pages 131-137
    Published: 1994
    Released on J-STAGE: April 10, 2006
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    Effects of highly selective δ-opioid receptor antagonists on the morphine-induced place preference in ddY and μ1-opioid receptor deficient CXBK mice were investigated. Pretreatment with naltrindole (NTI: a non-selective δ-opioid receptor antagonist), 7-benzylidenenaltrexone (BNTX: a selective δ1-opioid receptor antagonist) or naltriben (NTB: a selective δ2-opioid receptor antagonist) abolished the morphine-induced place preference in ddY mice in a dose-dependent manner. These findings suggest that the morphine-induced place preference may be mediated by both δ1 and δ2-opioid receptors. On the other hand, in μ1-opioid receptor deficient CXBK mice, pretreatment with these selective δ-opioid receptor antagonists did not affect the morphine-induced place preference, although pretreatment with β-funaltrexamine (β-FNA: a selective μ-opioid receptor antagonist) significantly inhibited the morphine-induced place preference. [D-Pen2, D-Pen5]enkephalin (DPDPE: a δ1-opioid receptor agonist) and [D-Ala2, Glu4]deltorphin (deltorphin II: a δ2-opioid receptor agonist) induced a significant place preference in ddY mice, but not in CXBK mice. These results suggest that δ1- and δ2-opioid receptors in the nucleus accumbens that are related to the DPDPE- and deltorphin II-induced place preference may be dysfunctional and/or poor in CXBK mice. These findings also indicate that δ1- and δ2-opioid receptors may be involved in the modulation of the reinforcing effect of morphine.
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  • Hideki Takase, Kazunori Yamamoto, Hiroyuki Hirano, Yuji Saito, Akira Y ...
    1994 Volume 66 Issue 1 Pages 139-147
    Published: 1994
    Released on J-STAGE: April 10, 2006
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    We studied the effects of marmin and nobiletin on the experimental acute gastric lesions, gastric transmucosal potential difference (PD) and gastric motor activity in rats and the contractions of isolated guinea pig ileum. Oral administration of marmin and nobiletin inhibited both the appearance of ethanol-induced gastric hemorrhagic lesions dose-dependently in a dose range of 10-50 mg/kg, with ED50 values for marmin and nobiletin being 17.2 and 8.0 mg/kg, respectively. However, marmin and nobiletin had minimal effects on aspirin-induced gastric lesions at a dose of 50 mg/kg, respectively. Marmin and nobiletin had no significant influence on the basal PD. Intragastrical administration of marmin and nobiletin at a dose of 25 mg/kg significantly prevented the PD reduction induced by ethanol. Both marmin and nobiletin given intragastrically at 25 mg/kg significantly inhibited gastric motor activity measured as intraluminal pressure recordings. Marmin and nobiletin exhibited concentration-dependent relaxations of contractions induced by acetylcholine, transmural electrical stimulation and histamine in isolated guinea pig ileum, respectively. These findings suggest that the anti-ulcer effects of marmin and nobiletin are ascribed primarily to the maintenance of the mucosal barrier integrity and inhibition of gastric motor activity and secondarily due to the prevention of the effects of endogenous acetylcholine and histamine.
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  • Toshio Obata, Yasumitsu Yamanaka
    1994 Volume 66 Issue 1 Pages 149-150
    Published: 1994
    Released on J-STAGE: April 10, 2006
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    Effects of some stresses on monoamine oxidase (MAO) activity in rat liver were investigated. Cold stress decreased MAO-A activity. Immobilization stress (IMMO) significantly decreased both MAO-A and MAO-B activities. The MAO-A/MAO-B ratio of the cold stress was significantly decreased, but IMMO was not significantly decreased. These results suggest that cold stress, but not IMMO may change the proportions of the multiple forms of MAO activity.
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  • Toshimasa Fujiwara, Shigetoshi Chiba
    1994 Volume 66 Issue 1 Pages 151-153
    Published: 1994
    Released on J-STAGE: April 10, 2006
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    We examined the effect of hypercholesterolemia on vasodilatory responses to clonidine in isolated and perfused rabbit common carotid arteries that had been preconstricted by phenylephrine. The responses decreased in rabbits fed an atherogenic diet for 4 or 8 weeks, whereas the responses to acetylcholine, nitroglycerin and substance P were not changed after the cholesterol feeding. Attenuated responses to clonidine were maintained for 24 weeks after cessation of the atherogenic diet, suggesting that this response might be an early marker of atherosclerosis.
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  • Toshimasa Fujiwara, Shigetoshi Chiba
    1994 Volume 66 Issue 1 Pages 155-157
    Published: 1994
    Released on J-STAGE: April 10, 2006
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    We investigated the effects of 2-methyl-5-HT and 1-phenylbiguanide on isolated and perfused rabbit common carotid arteries by a cannula insertion method. 1-Phenylbiguanide produced neither vasoconstriction nor dilation. On the other hand, 2-methyl-5-HT produced only a vasoconstriction, and the dose-response curve was shifted to the right in parallel by treatment with either ketanserin or bunazosin, although methysergide and granisetron had no antagonistic effect. Moreover, the vasoconstriction was not inhibited by guanethidine and imipramine. These data showed that 2-methyl-5-HT acts as an α1-adrenoceptor agonist but not as a 5-HT3-receptor agonist in this vessel.
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  • Tohru Masukawa, Kunio Nakanishi
    1994 Volume 66 Issue 1 Pages 159-161
    Published: 1994
    Released on J-STAGE: April 10, 2006
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    Dimethylthiourea (DMTU, 4.0 mmol/kg) injected into mice 30 min prior to alloxan injection markedly protected mice against the diabetogenic actions of 75 mg/kg alloxan. At 30 min after the above dose of DMTU alone (no alloxan), there was a marked rise in blood glucose. Mannoheptulose, an antagonist of glucose action at pancreatic β-cells, when given 24 min after DMTU and 6 min before alloxan, eliminated the DMTU-induced protection. The protection was also removed in the fasted mice in which DMTU did not cause hyperglycemia. These results indicate that DMTU protected mice from alloxan-induced diabetes by the indirect mechanism of producing hyperglycemia at the time of alloxan injection.
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  • Chiaki Kamei
    1994 Volume 66 Issue 1 Pages 163-165
    Published: 1994
    Released on J-STAGE: April 10, 2006
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    Morphine (5-20 mg/kg, s.c.) dose-dependently inhibited the hypothalamic self-stimulation response 1-2 hr after administration of the drug. Thereafter, slight increase in the self-stimulation response was seen 4-8 hr after drug administration. The depressant effect induced by 10 mg/kg, s.c. of morphine on the self-stimulation response was antagonized by 1 mg/kg, s.c. of levallorphan. Repeated administration of morphine (10 mg/kg, s.c.) resulted in an increase of the self-stimulation response. The self-stimulation response rate was increased significantly 24 and 48 hr after withdrawal of morphine in chronic-morphinetreated rats; In these rats, the initial dose of morphine (10 mg/kg, injected s.c. twice daily 7 days a week) was increased gradually until at the end of 5 weeks, each dose was 50 mg/kg, s.c.
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