BENZAMIDE DERIVATIVES PROVIDE EVIDENCE FOR THE INVOLVEMENT OF A 5-HT4 RECEPTOR TYPE IN THE MECHANISM OF ACTION OF SEROTONIN IN FROG ADRENOCORTICAL-CELLS

被引:61
作者
IDRES, S [1 ]
DELARUE, C [1 ]
LEFEBVRE, H [1 ]
VAUDRY, H [1 ]
机构
[1] UNIV ROUEN HAUTE NORMANDIE,FAC SCI,CNRS,URA 650,RECH ENDOCRINOL MOLEC GRP,BP 118,F-76134 MT ST AIGNAN,FRANCE
来源
MOLECULAR BRAIN RESEARCH | 1991年 / 10卷 / 03期
关键词
SEROTONIN; SEROTONIN RECEPTOR; CAMP; BENZAMIDE DERIVATIVE; CORTICOSTEROID SECRETION; FROG ADRENAL GLAND PERIFUSION;
D O I
10.1016/0169-328X(91)90068-9
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We have previously shown that serotonin (5-HT) is a potent stimulator of corticosterone and aldosterone secretion by frog adrenocortical cells and we have demonstrated that the action of 5-HT is not mediated by the classical 5-HT receptor subtypes i.e. 5-HT1, 5-HT2 and 5-HT3. Recently, a non-classical 5-HT receptor (termed 5-HT4) has been characterized using 4-amino-5-chloro-2-methoxy-benzamide derivatives as serotonergic agonists. In the present report, we have investigated the possible involvement of the 5-HT4 receptor subtype in the mechanism of action of 5-HT on steroid secretion. Increasing concentrations of benzamide derivatives (zacopride, cisapride and BRL 24924) gave rise to a dose-related stimulation of corticosteroid production, zacopride being the most potent compound of this series to enhance steroidogenesis. Prolonged administration (230 min) of zacopride induced a rapid increase in corticosterone and aldosterone output followed by a gradual decline of corticosteroid secretion. During prolonged exposure of adrenal tissue to zacopride (10(-5) M), the corticotropic activity of 5-HT (10(-6) M) was totally abolished. The stimulatory effects of 5-HT and zacopride were abolished by the non-selective 5-HT3 antagonist ICS 205 930. In contrast methysergide, a 5-HT1 receptor antagonist, and MDL 72222, a selective 5-HT3 antagonist did not block zacopride-induced corticosteroid secretion. Both 5-HT and zacopride induced a dose-related increase in cAMP production by frog adrenal slices. Taken together, these results indicate that the stimulatory effect of 5-HT on frog adrenocortical tissue is mediated by activation of a 5-HT4 receptor subtype positively coupled to adenylate cyclase.
引用
收藏
页码:251 / 258
页数:8
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