EFFECTS OF GABA ANTAGONISTS AND STRUCTURAL GABA ANALOGS ON BACLOFEN STIMULATED GASTRIC-ACID SECRETION IN THE RAT

被引:16
作者
HARA, N
HARA, Y
GOTO, Y
机构
[1] TOKUSHIMA BUNRI UNIV,DEPT PHARMACOL,YAMASHIRO CHO,TOKUSHIMA 770,JAPAN
[2] SUMITOMO PHARMACEUT CO LTD,RES LABS,KONOHANA KU,OSAKA 554,JAPAN
关键词
D O I
10.1254/jjp.52.345
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The effects of GABA receptor antagonists (bicuculline and phaclofen) and structural GABA-analogues on baclofen stimulated gastric acid secretion were studied in standardized perfused rat stomach preparations. Pretreatment with bicuculline, a GABAA-receptor antagonist, in the doses of 1 and 3 mg/kg, subcutaneously, had no influence on the gastric acid response to baclofen. In addition, phaclofen. a GABAB antagonist, in the doses of 3 to 30 mg/kg, intravenously, was found to have no significant effect on the acid response to baclofen. However, GABA-anlaogues (MOPS and ABA; 10-30 mg/kg, i.v.) and lipophilic GABA derivatives structurally related to beta-amino acids (APPA and APHA; 30 mg/kg, i.v.) significantly counteracted the secretagogue action of baclofen. Further experiments on APPA action showed that the antisecretory effect of APPA could be overcome by higher doses of baclofen. APPA did not affect bethanechol stimulated acid secretion. These results suggest that the secretagogue action of baclofen is independent to GABAA- and GABAB-receptors and that APPA may interact with baclofen in regulation mechanisms of acid secretion, although further investigations are necessary to define the mode of action of APPA on the GABA-ergic system. © 1990, The Japanese Pharmacological Society. All rights reserved.
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页码:345 / 352
页数:8
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