THE LONG-ACTING VASOACTIVE INTESTINAL POLYPEPTIDE AGONIST RO-25-1553 IS HIGHLY SELECTIVE OF THE VIP2 RECEPTOR SUBCLASS

RO 25-1553 is a synthetic VIP analogue that induced a longlasting rela xation of tracheal and bronchial smooth muscles as well as a reduction of edema and eosinophilic mobilization during pulmonary anaphylaxis. In the present study, we tested in vitro the capacity of RO 25-1553 to occupy the different VIP/PACAP receptor subclasses and to stimulate a denylate cyclase activity. The cellular models tested expressed one si ngle receptor subtype: Chinese hamster ovary (CHO) cells transfected w ith the rat recombinant PACAP I, rat VIP1, and human VIP2 receptors; S UP T1 cells expressing the human VIP2 and HCT 15 and LoVo cells expres sing the human VIP1 receptor. RO 25-1553 was threefold more potent tha n VIP on the human VIP2 receptor, 100- and 600-fold less potent than V IP on the rat and human VLP1 receptors, respectively, and 10-fold less potent than VIP and 3000-fold less potent than PACAP on the PACAP I r eceptor. RO 25-1553 was a full agonist on the VIP2, the PACAP I, and t he rat recombinant VIP1 receptor but a partial agonist only on the hum an VIP1 receptor. Thus, RO 25-1553 is a highly selective agonist ligan d for the VIP2 receptor subclass. (C) 1997 Elsevier Science Inc.