Functional splice variants of the type II G protein-coupled receptor (VPAC2) for vasoactive intestinal peptide in mouse and human lymphocytes.

A PCR-based search for splice variants of the VPAC2 G protein-coupled receptor for vasoactive intestinal peptide (VIP) revealed: (a) a short-deletion variant in mouse lymphocytes termed VPAC2de367-380, that lacks 14 amino acids in the seventh transmembrane domain, and (b) a long-deletion variant in human lymphocytes termed VPAC2de325-438(i325-334), that lacks 114 amino acids beginning with the carboxyl-terminal end of the third cytoplasmic loop and has 10 new carboxy-terminal amino acids. VPAC2de367-380 binds VIP normally, but shows reduced VIP-evoked signaling and effects on immune functions, whereas VPAC2de325-438(i325-334) shows reduced binding affinity for VIP and a complex pattern of functional differences. These splice variants may modify the immunoregulatory contributions of the VIP-VPAC2 axis.