In vitro properties of a high affinity selective antagonist of the VIP1 receptor

被引：154

作者：

Gourlet, P ^{[1
]}

De Neef, P ^{[1
]}

Cnudde, J ^{[1
]}

Waelbroeck, M ^{[1
]}

Robberecht, P ^{[1
]}

机构：

[1] Free Univ Brussels, Fac Med, Lab Chim Biol & Nutr, Med Sch,Dept Biochem & Nutr, B-1070 Brussels, Belgium

来源：

PEPTIDES | 1997年 / 18卷 / 10期

关键词：

VIP receptors; VIP antagonists;

D O I：

10.1016/S0196-9781(97)00230-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A selective high affinity VIP1 receptor antagonist [Acetyl-His(1), D-Phe(2), Lys(15) Arg(16), Leu(17)] VIP(3-7)/GRF(8-27) or PG 97-269 was synthesized, by analogy with recently obtained selective VIP1 receptor agonists. The properties of the new peptide were evaluated on Chinese hamster ovary (CHO) cell membranes expressing either the rat VIP1-, rat VIP2- or the human VIP2-recombinant receptors and on LoVo cell membranes expressing exclusively the human VIP1 receptor. The IC50 values of I-125-VIP binding inhibition by PG 97-269 were 10, 2000, 2 and 3000 nM on the rat VIP1-, rat VIP2-, human VTP1- and human VIP2 receptors, respectively. PG 97-269 had a negligible affinity for the PACAPI receptor type. It did not stimulate adenylate cyclase activity, but inhibited competitively effect of VIP on the VIP1 receptor mediated stimulation of adenylate cyclase activity. The K-i values were respectively of 15 +/- 5 nM and 2 +/- 1 nM for the rat and human VLP1 receptors. Thus the described molecule in the first reported VIP antagonist with an affinity in the nM range and with a high selectivity for the VIP1 receptor subclass. It map be useful for evaluation of the physiological role of VIP in rat and human tissues. (C) 1997 Elsevier Science Inc.

引用

页码：1555 / 1560

页数：6

共 37 条

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