IN-VITRO PROPERTIES OF A HIGH-AFFINITY SELECTIVE ANTAGONIST OF THE VIP1 RECEPTOR

A selective high affinity VIP1 receptor antagonist [Acetyl-His(1), D-P he(2), Lys(15) Arg(16), Leu(17)] VIP(3-7)/GRF(8-27) or PG 97-269 was s ynthesized, 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-, ra t VIP2- or the human VIP2-recombinant receptors and on LoVo cell membr anes expressing exclusively the human VIP1 receptor. The IC50 values o f 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 recep tor type. It did not stimulate adenylate cyclase activity, but inhibit ed competitively effect of VIP on the VIP1 receptor mediated stimulati on 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 af finity in the nM range and with a high selectivity for the VIP1 recept or subclass. It map be useful for evaluation of the physiological role of VIP in rat and human tissues. (C) 1997 Elsevier Science Inc.