A Cloned Frog Vasoactive Intestinal Polypeptide/ Pituitary Adenylate Cyclase-Activating Polypeptide Receptor Exhibits Pharmacological and Tissue Distribution Characteristics of Both VPAC1 and VPAC2 Receptors in Mammals

• DOI: 10.1210/en.140.3.1285
• Publication Date: 2004-02-24T00:18:04Z
• Authors: D. Alexandre
• Keywords: Secretin

Three receptor subtypes for the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) have been identified in mammals: PAC1 (PAC1-R) which is selectively activated by PACAP, two VPAC receptors (VPAC1-R VPAC2-R), are equally stimulated PACAP VIP. The structures of VIP well conserved during evolution, but little known about VIP/PACAP nonmammalian species. An amphibian complementary DNA (cDNA) has cloned characterized from a frog (Rana ridibunda) cDNA library. predicted protein contains seven putative transmembrane domains exhibits highest sequence identity (65%) with human VPAC1-R. was transiently expressed LLC-PK1 cells, its pharmacological profile determined comparison Both cAMP accumulation through an EC50 30 nm. In contrast, secretin, at concentrations that stimulate VPAC1-R, had no effect on production. RT-PCR analysis revealed widespread distribution this peripheral tissues. situ hybridization histochemistry using RNA probe showed gene highly several hypothalamic thalamic nuclei to lesser extent pallium striatum. pituitary, messenger levels were detected distal lobe. Taken together, these data show shares common features both VPAC1-R VPAC2-R mammals; mammalian lack secretin brain reminiscent characteristics VPAC2-R. should thus prove useful decipher structure-activity relationships family.