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Volume 95, Issue 1
Displaying 1-6 of 6 articles from this issue
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Shuji UCHIDA, Hiroshi YOSHIDA1990 Volume 95 Issue 1 Pages 7-14
Published: 1990
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSSince acetylcholine (ACh) was identified as a neurotransmitter at parasympathetic nerve terminals by pioneering pharmacologists such as O. Schmiedeberg, R. Hunt, O. Loewi and H.H. Dale, muscarinic acetylcholine receptors (mACh-R) serving as a transducer of muscarinic action have been assumed to exist. After many tries to identify the mACh-R, it's existence was established by the group of S.H. Snyder, who employed binding assays with the radioligand 3H-QNB. The presence of a neuronal (M1) and a peripheral (M2) mACh-R was suggested from the action of an M1-specific agonist, McN-A-343; and this observation was followed by the discovery that the antagonist pirenzepine had higher affinity for M1 than for M2. Later, peripheral mACh-Rs were further subclassified in two types by the heart-specific action of gallamine and the different affinities of AF-DX116 and 4-DAMP. At present, three subtypes, M1 (neuronal), M2 (heart) and M3 (other peripheral organs), can be pharmacologically distinguished by affinity differences. On the other hand, purification of mACh-R and analysis by gene technology revealed the presence of five mACh-R mRNAs (m1-m5), which were expressed in various organs with different abundances. These subtypes couple with subcellular muscarinic responses through different GTP-binding proteins. The connection between the subtypes, GTP-binding proteins and responses is not fully understood yet. Our studies showed that in guinea pig heart, in which only m2 mRNA is expressed, muscarinic agonists recognize two subgroups (M2α and M2β) with different affinities. One couples with the inhibition of adenylate cyclase, and the other couples with PI turnover through different GTP-binding proteins. These results indicate that the subtypes can be subclassified further with posttranslational protein modification.View full abstractDownload PDF (6661K) -
Takeshi OMATA, Hajime INOUE, Yoshiyuki SEYAMA, Saburo YAMASHITA1990 Volume 95 Issue 1 Pages 15-20
Published: 1990
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSIn order to elucidate the action of an H2 blocker (cimetidine) and gastric mucosal protection agents (sucralfate and sofalcone) on the relapse and recurrence of gastric ulcer, the effects of cimetidine, sucralfate and sofalcone on the contents of histamine and serotonin and histidine decarboxylase (HDC) activity in the gastric mucosa were examined in the ulcer region and the intact region at the 10th day after the operation to produce acetic acid-induced gastric ulcer in rats. The following results were obtained: 1) HDC activity in the gastric mucosa of rats treated with cimetidine (100 mg/kg twice daily) tended to increase in the intact region, and it was significantly increased in the ulcer region. 2) Increased HDC activity due to cimetidine treatment was observed at the 10th day after interruption of cimetidine administration. 3) The HDC activity in the gastric mucosa was not changed by the treatment with sucralfate (500 mg/kg/day) and sofalcone (200 mg/ kg/day). The results suggest that the increased HDC activity in the gastric mucosa might participate in the relapse and recurrence of gastric ulcer after discontinuation of cimetidine administration.View full abstractDownload PDF (4303K) -
Yasuo TAKEHANA, Shuichiro HAMANO, Shinji KIKUCHI, Hiroshi KUSAMA, Hide ...1990 Volume 95 Issue 1 Pages 21-30
Published: 1990
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSWe studied the inhibitory effects of OKY-046·HCl on PAF-induced airway hyperresponsiveness (AHR) in guinea pigs. (1) Inhalation of PAF (1 or 10 μg/ml) caused AHR to acetylcholine (ACh) aerosol and increased TXB2 generation in broncho-alveolar lavage fluid (BALF) at 30 min and 60 min, but the AHR and the TXB2 generation disappeared at 2 hr. OKY-046·HCl (100 mg/kg, intraduodenally) inhibited the AHR, which was accompanied by its inhibition of the TXB2 generation. However, no changes of 6-keto-PGF1α in BALF were found. (2) There were no changes in the number of leukocytes; the activities of alkaline phosphatase, N-acetyl-β-D-glucosaminidase, and lactate dehydrogenase; and the LTC4/D4/E4 in BALF. (3) In bronchus-lung preparations, PAF (1 μg/min) also caused the AHR and increased TXB2 generation. OKY-046·HCl (100 μg/min) inhibited the AHR and TXB2 generation. (4) PAF (1 μg/ml) evoked TXB2 generation in BALF from normal guinea pigs. OKY-046·HCl (10-4 M) inhibited its increase. (5) Stable TXA2 (STA2, 1 ng/ml) inhalation also caused AHR to ACh at 30 min. STA2 (0.45 ng/min) also caused the AHR in bronchus-lung preparations. These results suggest that OKY-046·HCl can inhibit PAF-induced AHR by suppressing the generation of TXA2. We also supposed that TXA2 is released from lung parenchyma, airway epithelium and cell components in BALF.View full abstractDownload PDF (7323K) -
Hiroyuki MIZUNO, Yoshinori TAKAHASHI, Hiromitsu OHNO, Miwa MISAWA1990 Volume 95 Issue 1 Pages 31-40
Published: 1990
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSEffects of flutropium bromide, a new bronchodilator with an anticholinergic action, alone or in combination with other antiasthma drugs were investigated in guinea pigs by using an index of inhibition of the acetylcholine (ACh)-induced bronchoconstriction. Single inhalation of flutropium bromide (0.0003%) into the airways of guinea pigs inhibited the ACh (i.v.)-induced bronchoconstriction without changing the fall in blood pressure induced by ACh. When salbutamol (3 μg/kg, i.v.), aminophylline (5 mg/kg, i.v.) or disodium cromoglycate (10 mg/kg, i.v.) was administered in combination with flutropium bromide (0.0003%), bronchodilation was enhanced as compared with single administration of the respective antiasthma drugs. From the above results, it is indicated that inhalation of flutropium bromide provides a more efficient bronchodilation in combination with other antiasthma drugs that possess different mechanisms of antiasthma effects.View full abstractDownload PDF (7409K) -
Tomoaki TAMURA, Junko OGAWA, Toshietsu TANIGUCHI, Isami WAKI1990 Volume 95 Issue 1 Pages 41-46
Published: 1990
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSActions of eptazocine, a novel analgesic, on isolated smooth muscle preparations were investigated. Eptazocine (10-5M) slightly inhibited electrically-driven twitch-tension in guinea pig ileum preparations sensitive to μ- and κ-agonists, and this effect was antagonized by 10-7M naloxone. Eptazocine (10-5 ?? 10-4 M) inhibited such an effect by the μ-agonist morphine. In mouse vas deferens preparations havingδ-, μ- and κ-receptors, eptazocine (10-7 M ??) inhibited the twitch-tension in a dose-dependent manner, being hardly inhibited by naloxone. On the other hand, MR-2266 (10-6M), a relatively selective κ-receptor antagonist, inhibited the eptazocine effect. The Ke (equilibrium dissociation constant) value of naloxone against eptazocine was 325 nM and the Ke value of MR-2266 against eptazocine was 33.2 nM, showing that MR-2266 was 9.79-fold more effective than naloxone. These results suggest that eptazocine acted as a μ-receptor antagonist and as a κ-receptor preferential agonist in isolated smooth muscle preparations.View full abstractDownload PDF (4687K) -
[in Japanese]1990 Volume 95 Issue 1 Pages 47-48
Published: 1990
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSDownload PDF (1760K)
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