The 5-HT4 receptor antagonist ML10375 inhibits the constitutive activity of human 5-HT4(c) receptor

被引：29

作者：

Blondel, O

Gastineau, M

Langlois, M

Fischmeister, R ^{[1
]}

机构：

[1] Univ Paris Sud, ISIT, IFR, Inst Signalisat & Innovat Therapeut, F-92296 Chatenay Malabry, France

[2] Univ Paris Sud, INSERM, Lab Cardiol Cellulaire & Mol, U446, F-92296 Chatenay Malabry, France

[3] Univ Paris Sud, Lab Reconnaissance Mol & Cellulaire, CNRS, BIOCIS,URA 1843,Fac Pharm, F-92296 Chatenay Malabry, France

来源：

BRITISH JOURNAL OF PHARMACOLOGY | 1998年 / 125卷 / 04期

关键词：

human; serotonin; 5-HT4; receptors; inverse agonist; ML10375;

D O I：

10.1038/sj.bjp.0702163

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Transient expression in COS-7 cells of the recombinant human 5-hydroxytryptamine (5-HT) h5-HT4(c) receptor isoform led to constitutive activity of the receptor. The 5-HT4 receptor antagonist 2-(cis-3,5-dimethylpiperidino)ethyl 4-amino-5-chloro-2-methoxybenzoate (ML10375) at 1 mu M completely abolished the 5-HT (1 mu M)-mediated increase in adenylyl cyclase activity in COS-7 cells expressing the h5-HT4(c) receptor. Moreover, ML10375 also reduced basal cAMP levels in cells over-expressing the receptor, even in the absence of agonist. The inhibitory effect of ML10375 on basal adenylyl cyclase activity was not modified by pre-treatment of the cells with pertussis toxin, indicating that ML10375 acts through inactivation of spontaneously active h5-HT4(c), receptors rather than through a G(i)/G(o) regulatory pathway. We conclude that ML10375 acts as an inverse agonist on the h5-HT4(c) receptor.

引用

页码：595 / 597

页数：3

共 11 条

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