Two receptors for vasoactive intestinal polypeptide with similar specificity and complementary distributions

Abstract

Vasoactive intestinal polypeptide (VIP) has a variety of physiological effects. Pharmacological evidence suggesting that VIP acts via multiple receptors has been confirmed by the cloning of two VIP receptors (VIP1 and VIP2) with very different amino acid sequences. At both the VIP1 and the VIP2 receptor VIP, PHI, PACAP38, and PACAP27 have similar potency to each other. Only the VIP1 receptor is activated by secretin. The messenger RNAs (mRNAs) for the two receptors have completely different distributions as mapped by in situ hybridization histochemistry. VIP1 receptor mRNA is predominantly found in the lung, small intestine, thymus, and within the brain in the cerebral cortex and hippocampus. VIP2 receptor mRNA is present in a number of areas where VIP acts but VIP1 receptor mRNA is not present, including the stomach and testes. In the CNS VIP2 receptor mRNA is exclusively present in areas associated with neuroendocrine function, including several hypothalamic nuclei. In the periphery, it is also present in the pituitary and in pancreatic islets.

Effects of Centrally Administered Pituitary Adenylate Cyclase-Activating Polypeptide on c-<i>fos</i> Gene Expression and Heteronuclear RNA for Vasopressin in Rat Paraventricular and Supraoptic Nuclei

“…Some peripheral actions of PACAP, such as the vasodilating effect, are similar to those of VIP and mediated via the VIP receptor [37, 38]. The VIP receptor, which has a similar affinity for PACAP and VIP [14], is identified in the PVN and the SON [39]. In the present study, it is interesting that administration of VIP induced a clearer upregulation of c- fos transcripts in the SON than the PVN.…”

Vasoactive Intestinal Peptide (VIP) and VIP Receptors-Elucidation of Structure and Function for Therapeutic Applications

“…VPAC1 is expressed in the liver, lungs, kidneys, prostate gland, mammary glands, spleen, lymphocytes, mucosa of the stomach and small intestine, and many other tissues [16]. In the central nervous system, VPAC1 is expressed in the cerebral cortex, piriform cortex, dentate gyrus, lateral amygdaloid nucleus, putamen, supraoptic nucleus, choroid plexus, and pineal body, and other regions [17]. VPAC2 is expressed in large amounts in the smooth muscle of organs and vascular walls and is also observed in the large intestinal mucosa, thyroid follicular cells, adrenal medulla, retina, and alveolar epithelium.…”

“…In the central nervous system, VPAC2 is expressed in the cerebral cortex, olfactory brain, thalamus, hippocampus, amygdala, paraventricular cortex, etc. [17]. VPAC2 is also expressed in lymphocytes and macrophages after bacterial or viral infections [2].…”

Effect of Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-Activating Polypeptide on Pancreatic, Hepatic and Duodenal Mucosal Bicarbonate Secretion in the Pig

“…In contrast, the VPAC 1 /VPAC 2 receptors are present in many tissues outside the CNS including the liver [9, 10], duodenal and small intestinal epithelium [11, 12]and pancreatic acini [13]. Usdin et al [14]tried to distinguish between VPAC 1 /VPAC 2 receptors using specific messenger RNA (mRNA) probes. They identified only VPAC 2 (and not VPAC 1 ) receptor mRNA in duodenal muscular layers, duodenal mucosa and epithelium.…”

“…They identified only VPAC 2 (and not VPAC 1 ) receptor mRNA in duodenal muscular layers, duodenal mucosa and epithelium. Both VPAC 1 /VPAC 2 receptor mRNA was identified in the pancreas [14]. mRNA for both VPAC 1 /VPAC 2 receptors was lightly scattered throughout the liver parenchyma, perhaps indicating a slight non-specific absorption to the tissue [14].…”