The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
62 巻, 2 号
選択された号の論文の14件中1~14を表示しています
  • Masayuki Uchida, Shingo Yano, Kazuo Watanabe
    1993 年 62 巻 2 号 p. 123-129
    発行日: 1993年
    公開日: 2006/04/12
    ジャーナル フリー
    The effect of capsaicin-sensitive nerve degeneration (capsaicin-treatment) on the corpus and the antrum was investigated in the absolute ethanol-induced lesion model in rats. The gastric lesions in the antrum were significantly aggravated by the capsaicin-treatment, while those in the corpus were not affected. To clarify the different susceptibility between the antrum and the corpus, the effects on gastric mucosal blood flow (GMBF), mucus secretion and levels of calcitonin gene-related peptide (CGRP) or substance P (Sub P), were investigated by the hydrogen gas clearance method, histochemical methods and immunohistochemical methods, respectively. The GMBF in the antrum was significantly decreased by the capsaicin-treatment, but that in the corpus was not. Moreover, capsaicin-treatment increased the mucus secretion in the antrum, but not in the corpus. Capsaicin-treatment significantly decreased CGRP and Sub P-immunoreactive substances in the vascular smooth muscle in the antrum, but not in the corpus. On the 4th day after absolute ethanol, antral ulcers were observed. From the above results, it was suggested that capsaicin-treatment decreased the gastroprotective ability in the antrum to a greater extent than in the corpus and this may be caused by the decrease of GMBF through the decrease of CGRP- and Sub P-immunoreactive substances.
  • Katsuhiko Sakitama
    1993 年 62 巻 2 号 p. 131-136
    発行日: 1993年
    公開日: 2006/04/12
    ジャーナル フリー
    The effects of intrathecal noradrenaline (NA) on the flexor reflex mediated by group II afferent fibers (group II flexor reflex) were investigated in anesthetized spinal rats. Low doses (0.01 and 0.1 μmol) of NA-HCl inhibited the group II flexor reflex, while high doses (1 and 10 μmol) facilitated it. In rats pretreated with the selective α2-antagonist yohimbine-HCl (0.1 μmol), the effect of NA-HCl (0.1 μmol) shifted from inhibition to facilitation. Intravenous administration of prazosin-HCl (0.1 and 1 mg/kg, i.v.), a selective α1-antagonist, dose-dependently antagonized the facilitation of the group II flexor reflex induced by NA-HCl in rats pretreated with yohimbine-HCl. The selective α2-agonist methoxamine-HCl (1 μmol) and the α2-agonist clonidine-HCl (0.1 μmol) facilitated and inhibited the group II flexor reflex, respectively. The effects of clonidine-HCl and methoxamine-HCl were almost the same as those of NA-HCl at doses of 0.1 and 10 μmol, respectively. NA-HCl (1 and 10 μmol) and methoxamine-HCl(1 μmol) increased the spontaneous electromyogram (EMG) spikes of the muscle tibialis anterior. The time course of the increase in the spontaneous EMG spikes was similar to that observed in the group II flexor reflex. These results suggest that NA facilitates and inhibits the group II flexor reflex via α1- and α2-receptors, respectively, and one of the mechanisms of the facilitatory effects is the elevation of excitability of the α-motoneuron.
  • Tadayuki Saito, Asako Hagihara, Naoko Igarashi, Naomi Matsuda, Akira Y ...
    1993 年 62 巻 2 号 p. 137-143
    発行日: 1993年
    公開日: 2006/04/12
    ジャーナル フリー
    The inhibitory effects of emedastine difumarate on histamine release were studied in rat peritoneal mast cells. Emedastine significantly inhibited substance P (SP)-induced histamine release at concentrations above 10-9 M in the presence of extracellular Ca2+ and at concentrations above 10-11 M in its absence. At concentrations of 10-8 M or higher, emedastine significantly inhibited SP-induced Ca2- release from intracellular Ca stores and SP-induced 45Ca uptake into mast cells. Emedastine also inhibited passive peritoneal anaphylaxis in rats and guinea pigs. We conclude that the clinical antiallergic effects of emedastine involve the inhibition of histamine release and that this inhibition is mediated by the inhibition of Ca2+ release from intracellular Ca stores and the inhibition of Ca2+ influx into mast cells.
  • Yasuhiro Akiyama, Kuniko Hara, Isao Ohkawa, Tetsuya Tajima
    1993 年 62 巻 2 号 p. 145-153
    発行日: 1993年
    公開日: 2006/04/12
    ジャーナル フリー
    ABSTRACT-The effects of menatetrenone, a vitamin K2 homologue, on bone loss induced by ovariectomy in rats were studied in 3 experiments. Menatetrenone was given as a dietary supplement. In experiment 1, at 2 weeks postovariectomy, menatetrenone (10 mg/kg/day given for 2 weeks) inhibited the decrease in bone density of the femoral metaphysis induced by the ovariectomy. In experiment 2, menatetrenone (3 or 30 mg/kg/day given for 6 months) inhibited the decrease in bone strength of the femur and the decrease in calcium and hydroxyproline content of the femoral diaphysis at 6 months postovariectomy. In experiment 3, menatetrenone treatment, at 30 or 100 mg/kg/day for 6 months, protected against the decrease in bone strength and calcium and hydroxyproline content in the bone loss model induced by ovariectomy and calcium-deficient diet. These findings suggest that menatetrenone protects against the bone loss induced by ovariectomy.
  • Jun Tamaoki, Atsushi Chiyotani, Kiyoshi Takeyama, Toshinori Kanemura, ...
    1993 年 62 巻 2 号 p. 155-159
    発行日: 1993年
    公開日: 2006/04/12
    ジャーナル フリー
    To determine the effects of the Kampo drugs Saiboku-to, Bakumondo-to and Orengedoku-to on β-adrenergic function in airway smooth muscle, we studied isolated canine bronchial segments under isometric conditions in vitro. Incubation of tissues with these drugs did not alter the contractile responses to acetylcholine and histamine. The relaxation of tissues precontracted with acetylcholine induced by isoproterenol was augmented by Saiboku-to and Bakumondo-to, so that the concentration of isoproterenol required to produce a half-maximal effect (IC50) was decreased from 4.6±0.5 × 10-8 M to 1.9± 1.0 × 10-8 M (P<0.05) and to 1.0±0.8 × 10-8 M (P<0.01), respectively, whereas Orengedoku-to had no effect. These effects were concentration-dependent with the threshold concentrations being 0.3 mg/ml for Saiboku-to and 0.1 mg/ml for Bakumondo-to. Saiboku-to and Bakumondo-to did not affect cyclic AMP levels in airway smooth muscle per se but potentiated the isoproterenol-induced cyclic AMP accumulation. These results suggest that Saiboku-to and Bakumondo-to but not Orengedoku-to potentiate β-adrenergic function in airway smooth muscle, which may reflect the efficacy of these drugs on airway hyperresponsiveness and asthma.
  • Kuei-Sen Hsu, Jaw-Jou Kang, Shoei-Yn Lin-Shiau
    1993 年 62 巻 2 号 p. 161-168
    発行日: 1993年
    公開日: 2006/04/12
    ジャーナル フリー
    The purpose of this investigation was to explore the possible mechanism of muscle contracture and twitch depression induced by arsenite in the mouse diaphragm. Arsenite-contracture was dependent on extracellular Ca2+; both EGTA and Ca2+-channel blockers (nifedipine and verapamil) inhibited arsenite-contracture. However, the activators caffeine and ryanodine and the inhibitor ruthenium red of the Ca2+ releasing channel of sarcoplasmic reticulum (SR) all exerted a profound inhibitory action on arsenite-contracture. Neither the Ca2+-release nor the Ca2+-ATPase activity of SR. were affected by 50 μM arsenite. These findings indicate a possibility that arsenite induced muscle contracture by enhancing Ca2+-entry which further induced Ca2+-release from SR. Moreover, the possible mechanism of twitch blockade induced by arsenite was studied by an electrophysiological technique. The frequency of miniature endplate potential (m.e.p.p.) was initially increased but eventually abolished by arsenite, while the amplitude of m.e.p.p. remained unaffected and that of endplate potential rapidly declined. It is considered that arsenite increased the spontaneous release of transmitter by enhancing Ca2+ entry into the nerve terminal and inhibited the evoked transmitter release possibly by acting at a certain site which governs transmitter release.
  • Yutaka Ito, Susumu Nakamura, Yuichi Onoda, Yoichi Sugawara, Osasi Taka ...
    1993 年 62 巻 2 号 p. 169-174
    発行日: 1993年
    公開日: 2006/04/12
    ジャーナル フリー
    To investigate the mechanism of the anti-peptic action of ecabet sodium (TA-2711) observed in pylorus-ligated rats, effects of this drug on the peptic activity of rat gastric juice, purified hog pepsin and pepsinogen were studied in vitro. After incubation with or without ecabet at acidic pH, the reaction mixture was centrifuged, and the peptic activity of the supernatant was measured. Ecabet depressed the peptic activity of pepsin and pepsinogen in parallel with a decrease in the protein concentration of the respective super natant. Depression was greatest with pepsinogen (97% at 2.5 mg/ml of the drug) followed by gastric juice (about 60% at 10 mg/ml), and inhibition of the peptic activity of pepsin was weakest (about 10% at 10 mg/ml). When a fraction of the rat gastric juice containing substances with molecular weights below 10, 000 was added to the pepsin solution, the anti-peptic activity of ecabet was potentiated. These results suggest that oral dosing of ecabet reduces the peptic activity of gastric juice by precipitating pepsin, which is facilitated by an unknown component(s) of gastric juice, and that the inactivation of pepsinogen may also contribute to the anti-peptic activity of ecabet.
  • Yutaka Ito, Yuichi Onoda, Susumu Nakamura, Kouzo Tagawa, Takeshi Fukus ...
    1993 年 62 巻 2 号 p. 175-181
    発行日: 1993年
    公開日: 2006/04/12
    ジャーナル フリー
    To define the mechanism of the protection by ecabet (TA-2711) of the gastric mucosa from peptic attack, the characteristics of protein binding of this drug and its effect on peptic hydrolysis of substrate proteins were investigated in vitro. Both the binding to proteins and the hydrophobicity of ecabet were dependent on the pH; the lower the pH, the higher both parameters. The percentage of ecabet bound to proteins was nearly constant, being independent of the drug concentration at pH''s below 2, indicating that this drug is bound to proteins in a non-specific manner. The activity of peptic hydrolysis of bovine serum albumin (BSA) decreased in the presence of ecabet, and this was not due to the interaction between pepsin and ecabet judging from the kinetic studies. The apparent Km values of peptic hydrolysis of BSA increased depending on the quantity of ecabet bound to BSA. These results suggest that ecabet is bound to substrate proteins by a non-specific hydrophobic interaction to form a complex that is less vulnerable to peptic hydrolysis.
  • Takashi Saito, Katsuro Shuto, Hisashi Kuribara, Sakutaro Tadokoro
    1993 年 62 巻 2 号 p. 183-190
    発行日: 1993年
    公開日: 2006/04/12
    ジャーナル フリー
    Behavioral effects of OM-853 were investigated in both mice and Mongolian gerbils. In mice, OM-853 alone produced no marked change in the ambulatory activity, although it tended to lower it at 100 mg/kg, and this drug (5-100 mg/kg, p.o.) reduced the ambulation-increasing effect of scopolamine (0.5 mg/kg, s.c.) in a dose-dependent manner. Moreover, OM-853 (50 and 100 mg/kg, p.o.) prolonged the latency times shortened by scopolamine under the passive avoidance. On the other hand, in the discrete avoidance situation, OM-853 facilitated the acquisition of shuttle avoidance at 10 and 25 mg/kg, p.o. and lever-press avoidance at 25 and 50 mg/kg, p.o. in the pre-training administration schedule, and the former at 25-100 mg/kg, p.o. and the latter at 10 and 25 mg/kg, p.o. in the post-training administration schedule. In gerbils, OM-853 (50 mg/kg, i.p.) ameliorated the learning deficit of the lever-press avoidance response induced by forebrain ischemia. The present results suggest that OM-853 has beneficial actions on some types of learning and memory in normal, scopolamine-treated and ischemic animals. The possible mechanisms involved are discussed.
  • Kazumi Takeya, Hiroaki Ando, Sawako Ando, Michio Yajima, Hirohiko Nomu ...
    1993 年 62 巻 2 号 p. 191-197
    発行日: 1993年
    公開日: 2006/04/12
    ジャーナル フリー
    The effect of vesnarinone (OPC-8212), an orally active positive inotropic agent was studied in tracheal muscle isolated from guinea pigs, and the mechanism of its action was analyzed. Vesnarinone (10-6 -10-4 M) caused a concentration-dependent relaxation of tracheal muscle pre-contracted by 10-4 M histamine. The potency of the relaxing effect of vesnarinone was greater than that of theophylline; the pD2 values for vesnarinone and theophylline were 4.9 and 4.5, respectively. Vesnarinone reduced the high-K+-induced contracture of depolarized tracheal muscle non-competitively (pD''2=3.7). Vesnarinone at the low concentration of 3 × 10-6 M shifted the concentration-response curve for isoproterenol in a parallel fashion to the left. Vesnarinone additively acted on the relaxing effect of isobutyl methyl xanthine. Propranolol (10-5 M) and reserpine pre-treatment (5 mg/kg, i.p., 24 hr) had no effect on the relaxing effect of vesnarinone. These results suggested that vesnarinone elevated the intracellular cyclic AMP level via phosphodiesterase inhibition, resulting in the tracheal muscle relaxation.
  • Hiroyuki Ohta, Kinzo Matsumoto, Hiroshi Watanabe, Mineo Shimizu
    1993 年 62 巻 2 号 p. 199-202
    発行日: 1993年
    公開日: 2006/04/12
    ジャーナル フリー
    Paeoniflorin, a major constituent of peony root (1 mg/kg, p.o.), attenuated scopolamine-induced deficit in radial maze performance. Both prazosin (0.5 mg/kg, i.p.) and yohimbine (0.3 mg/kg, i.p.) neither impaired radial maze performance by itself nor augmented the scopolamine-induced performance deficit. Prazosin significantly blocked the antagonizing effect of paeoniflorin on the scopolamine deficit, whereas yohimbine did not affect the paeoniflorin effect. These data suggest that the α1-adrenergic but not α2-adrenergic systems are involved in the antagonizing effect of paeoniflorin on the scopolamine deficit in radial maze performance in rats.
  • Naoyoshi Miura, Naoki Nakata, Yoshiaki Tanaka, Yoshihiro Hiraga, Yugo ...
    1993 年 62 巻 2 号 p. 203-206
    発行日: 1993年
    公開日: 2006/04/12
    ジャーナル フリー
    A novel serotonin reuptake inhibitor, (-)trans 4-(4-fluorophenyl)-3-(4-methoxyphenoxy-methyl)piperidine hydrochloride (FG-7080), was investigated for its effects on scopolamine-induced impairments in memory tasks of rats. In the radial-arm maze task, FG-7080 (3 mg/kg, p.o.) improved the impaired performance. FG-7080 (1 mg/kg, p.o.) administered before the acquisition trial reduced the acquisition deficits in the passive avoidance task. Thus, the compound showed improving effects in the appetitive and aversive memory tasks. These findings suggest that FG-7080 may ameliorate the cognitive impairments caused by the cholinergic dysfunction.
  • Hideki Okunishi, Yuko Oka, Naotaka Shiota, Tatsuhiko Kawamoto, Keifu S ...
    1993 年 62 巻 2 号 p. 207-210
    発行日: 1993年
    公開日: 2006/04/12
    ジャーナル フリー
    Using isolated arteries, we demonstrated a marked difference in the angiotensin II-forming systems between human and rodent vessels. In human arteries, only 30-40% of the conversion of angiotensin I to angiotensin II depended on the angiotensin-converting enzyme (ACE), and the rest of the angiotensin II formation was ascribed to chymostatin-sensitive angiotensin II-generating enzyme (CAGE). On the contrary, angiotensin II formation in rodent arteries totally depended upon ACE, without any sign of CAGE involvement. Such a marked species-difference can be relevant to the reported difference between humans and rodents in the ACE inhibitor effects on the myointimal hyperplasia after intimal balloon injury.
  • Yasuyuki Karasawa, Michael C. Koss
    1993 年 62 巻 2 号 p. 211-214
    発行日: 1993年
    公開日: 2006/04/12
    ジャーナル フリー
    Preganglionic stimulation of the thoracic sympathetic nerve trunk produced frequency-related decreases of ulnar arterial blood flow in the forepaw of anesthetized cats as measured by ultrasonic flowmetry. Vasoconstrictor responses were not altered by administration of propranolol or atropine. When given alone, both prazosin (3-100 μg/kg, i.v.) and rauwolscine (10-300 μg/kg, i.v.) produced only a modest reduction of sympathetic evoked vasoconstriction. However, extensive blockade was obtained when both antagonists were administered to the same animal. These results suggest that both α1- and α2-adrenoceptors coexist at postsynaptic sites in the vasculature of the cat paw and that neural activation of either type results in potent vasoconstriction.
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