VIP: Compound Profile

VIP is one of the most heavily referenced neuropeptides in the G protein-coupled receptor literature, which makes it a useful anchor point for how a class-B GPCR agonist is characterized in the lab. This profile covers what it is, the VPAC-receptor signaling the research attributes to it, and where it sits among the endogenous signaling neuropeptides. For the wider class, see the neuropeptides overview.

What is VIP?#

VIP, or vasoactive intestinal peptide, is a 28-residue linear neuropeptide first isolated from porcine intestine in the early 1970s and later mapped across the central and peripheral nervous systems. It belongs to the secretin/glucagon peptide superfamily and is closely related to PACAP, with which it shares two receptors. In its human form it is encoded by the VIP gene and processed from a larger precursor; research catalogs supply the mature synthetic 28-mer rather than the full prohormone. The identity anchor here is that mature sequence together with the UniProt record for the human precursor, since standalone supplier figures for salt form and net mass vary.

What does the research literature study?#

The mechanistic core of the VIP literature is receptor pharmacology. VIP binds two class-B G protein-coupled receptors, VPAC1 and VPAC2, which couple through Gs to adenylyl cyclase and raise intracellular cAMP; the IUPHAR review of the VIP/PACAP receptor family sets out how these receptors are defined, how VIP and PACAP overlap at them, and what pharmacological tools distinguish the subtypes. A companion account of VPAC receptor structure, molecular pharmacology, and accessory-protein interactions describes the binding determinants and signaling behaviour in cell-based models. Because VPAC receptors sit within the broader secretin-like receptor group, the structure-to-function review of PACAP and its receptors provides the comparative framework researchers use to place VIP among its relatives.

Beyond the receptor bench, two model systems recur. In the suprachiasmatic nucleus, a Nature Neuroscience study reported that VIP signaling supports rhythmicity and synchrony among mammalian clock neurons, which is why VIP appears throughout the circadian-network literature. And because VPAC signaling and cAMP output are relevant to receptor drug design, work on targeting VIP and PACAP receptor signaling examines how agonists and analogs at these receptors are approached in preclinical models. Across all of it, the framing is receptor mechanism and cellular signaling; this is preclinical research and does not speak to effects in people.

Where VIP sits in the neuropeptide class#

The neuropeptide class Nexara tracks spans engineered nootropic analogs and endogenous signaling peptides. VIP belongs firmly to the second group: a native, receptor-defined peptide studied for a well-characterized GPCR pathway rather than a designed fragment. That makes it a mechanistic counterpart to the Russian-developed pair Semax and Selank, which were built and stabilized from parent fragments for the laboratory. VIP instead descends directly from an endogenous molecule whose receptors and second-messenger pathway are unusually well mapped. Semax and Selank each carry their own compound profile (Semax, Selank) and a head-to-head in Semax vs Selank.

Handling and storage#

VIP is supplied as a lyophilized solid and dissolved prior to use. As a longer, basic linear peptide with a C-terminal amide, it is handled the same way as the rest of the catalog: the reconstitution primer covers solvent selection and avoiding aggregation, while the cold-chain article covers how stability changes once the powder is in solution.

Sources and further reading#

• VIP peptides, UniProt P01282: canonical record for the human VIP precursor and mature-peptide annotation.
• Pharmacology and functions of receptors for VIP and PACAP: IUPHAR review 1 (PMID 22289055): the reference account of the VPAC/PAC receptor family and how VIP is characterized at them. British Journal of Pharmacology 2012.
• VPAC receptors: structure, molecular pharmacology and interaction with accessory proteins (PMID 21951273): structural and molecular-pharmacology detail on the VIP receptors. British Journal of Pharmacology 2012.
• PACAP and its receptors: from structure to functions (PMID 10835102): the comparative receptor-family framework in which VIP is placed. Pharmacological Reviews 2000.
• VIP mediates circadian rhythmicity and synchrony in mammalian clock neurons (PMID 15750589): a preclinical study of VIP signaling in the suprachiasmatic-nucleus clock network. Nature Neuroscience 2005.
• Targeting VIP and PACAP receptor signaling (PMID 35897648): a review of how agonists and analogs at the VIP/PACAP receptors are approached in preclinical models. International Journal of Molecular Sciences 2022.