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Vasoactive intestinal polypeptide

Rodger A Liddle, MD
Section Editor
J Thomas Lamont, MD
Deputy Editor
Shilpa Grover, MD, MPH, AGAF


Vasoactive intestinal polypeptide (VIP) is a neuropeptide that functions as a neuromodulator and neurotransmitter. It is a potent vasodilator, regulates smooth muscle activity, epithelial cell secretion, and blood flow in the gastrointestinal tract [1-3]. As a chemical messenger, it functions as a neurohormone and paracrine mediator, being released from nerve terminals and acting locally on receptor-bearing cells.

The VIP receptor is a member of a unique class of G protein-coupled receptors. These receptors share a significant degree of sequence homology (>50 percent), which distinguishes them from members of the rhodopsin/beta-adrenergic family (class I) [4]. (See "Peptide hormone signal transduction and regulation".)


Like other gastrointestinal peptides, vasoactive intestinal polypeptide (VIP) is synthesized as a precursor molecule with a signal peptide containing 22 amino acids, which is then cleaved to the active peptide of 28 amino acids [5,6]. The gene encoding this peptide resides on chromosome 6 [7]. Some studies have demonstrated local control of VIP gene expression as VIP mRNA does not always parallel the peptide product [8]. These data suggest regulation at the post-transcriptional stage may be essential for normal VIP secretion [8].

The VIP peptide is remarkably well conserved across species and is identical in human, cow, pig, rat, dog, and goat species [3]. Even across species, amino acid substitutions are conservative and usually do not result in changes in bioactivity.

Alternative peptides derived from the VIP gene include peptide histidine isoleucine (PHI) [9], peptide histidine methionine [10,11], and peptide histidine valine [6]. Although the functional significance of these peptides is unclear, PHI is known to stimulate intestinal fluid secretion [12].

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Literature review current through: Nov 2017. | This topic last updated: Oct 08, 2015.
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