In Vitro Properties of a High Affinity Selective Antagonist of the VIP1 Receptor

Abstract Gourlet, P., P. De Neef, J. Cnudde, M. Waelbroeck and P. Robberecht. In vitro properties of a high affinity selective antagonist of the VIP 1 receptor. Peptides 18(10) 1555–1560, 1997.—A selective high affinity VIP 1 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 VIP 1 receptor agonists. The properties of the new peptide were evaluated on Chinese hamster ovary (CHO) cell membranes expressing either the rat VIP 1 -, rat VIP 2 - or the human VIP 2 - recombinant receptors and on LoVo cell membranes expressing exclusively the human VIP 1 receptor. The IC 50 values of 125 I-VIP binding inhibition by PG 97-269 were 10, 2000, 2 and 3000 nM on the rat VIP 1 -, rat VIP 2 -, human VIP 1 - and human VIP 2 receptors, respectively. PG 97-269 had a negligible affinity for the PACAP I receptor type. It did not stimulate adenylate cyclase activity, but inhibited competitively effect of VIP on the VIP 1 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 VIP 1 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 VIP 1 receptor subclass. It may be useful for evaluation of the physiological role of VIP in rat and human tissues.