VIP

Vasoactive intestinal peptide (VIP) is a 28-amino-acid neuropeptide (C147H237N43O43S, 3326.8 g/mol), first reported in 1970 as a vasodilatory gut peptide hormone. It is produced by lymphoid cells as well as by neural cells. VIP and the related pituitary adenylate cyclase-activating polypeptide (PACAP) are the primary endogenous stimuli for three class B G protein-coupled receptors: VPAC1, VPAC2 and PAC1. Splice-variant diversity in VIP, PACAP and their receptors has been reported to affect agonist selectivity, potency and signaling properties.

VIP in the research literature

Structural research has produced cryo-EM structures of VPAC1 and PAC1 in agonist-bound active states, and analyses of these structures have mapped molecular switches and interhelical interactions linked to agonist binding and receptor activation. In the gastrointestinal literature, VIP has been studied for its roles in ion secretion, nutrient absorption and gut motility, and genetic ablation of the peptide and its receptors in mice has been used to probe these pathways.

In the immune system, VIP acts through receptors on several immunocompetent cell types and has been reported to regulate production of pro- and anti-inflammatory mediators and expression of co-stimulatory molecules associated with Th1 and Th2 differentiation. In the mouse suprachiasmatic nucleus, intersectional genetics and real-time imaging showed that cells expressing VIP or VPAC2 are neurochemically and electrophysiologically distinct and together set ensemble circadian period and phase.