Endocrine Abstracts

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are important neuropeptides that are structurally related. They have been found to exert many physiological and pathophysiological effects through the activation of three specific receptors: PAC1R, VPAC1R, and VPAC2R. In tetrapods, PACAP and VIP are potent agonists to VPAC2R. In teleosts, we have previously identified a PHIR in goldfish which shares high level of sequence similarity with tetrapod VPAC2Rs. However, this PHIR does not interact with PACAP or VIP, while fish PHI was able to activate this receptor.

Here, we report the identification a full-length VPAC2R from an Actinopterygian, sturgeon (Acipenser schrenckii). This receptor contains 427 amino acid residues. In phylogenetic analysis, the receptor clusters with tetrapod VPAC2Rs and teleost PHIRs. Tissue distribution analysis by real-time PCR showed high levels of expression of this receptor is in gut and liver. Interestingly, after stable transfection into CHO-K1 cells, this receptor could be stimulated by human VIP, but not goldfish PHV or human PACAP as shown in functional cAMP assays. These data suggested that the ability of VPAC2R to bind PACAP was not found in sturgeon, a representative of an early jawed vertebrate (Gnathostomata), nor goldfish. This function of the receptor could be evolved after the teleost/tetrapod split and therefore is present only in the tetrapod lineage.