PACAP/VIP receptors in pancreatic beta-cells: their roles in insulin secretion

Ann N Y Acad Sci. 1996 Dec 26;805:44-51; discussion 52-3. doi: 10.1111/j.1749-6632.1996.tb17472.x.

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide belonging to the vasoactive intestinal polypeptide (VIP)/glucagon/secretin family. We have isolated a third PACAP receptor subtype, designated PACAPR-3, by molecular cloning. The cDNA encoding PACAPR-3 has been isolated from a mouse insulin-secreting beta-cell line MIN6 cDNA library. Mouse PACAPR-3 is a protein of 437 amino acids that has 50% and 51% identity with rat PACAP type I and type II receptors, respectively. We have expressed PACAPR-3 in mammalian cells and Xenopus oocytes. PACAPR-3 binds to VIP as well as PACAP-38 and -27, with a slightly higher affinity for PACAP-38, and is positively coupled to adenylate cyclase. PACAP-38, -27, and VIP evoked Ca2+ activated-Cl- currents in Xenopus oocytes. RNA blotting studies reveal that PACAPR-3 mRNA is expressed widely in tissues and cell lines, including pancreatic islets, insulin-secreting cell lines (MIN6, HIT-T15, and RINm5F), lung, brain, stomach, colon, and heart. Furthermore, insulin secretion from the MIN6 cells is stimulated significantly by PACAP-38 and VIP. The possible mechanisms of insulin secretion by PACAP and VIP are also discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cloning, Molecular
  • Female
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / physiology*
  • Mice
  • Molecular Sequence Data
  • Neuropeptides / pharmacology
  • Neurotransmitter Agents / pharmacology
  • Oocytes / physiology
  • Organ Specificity
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Rats
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
  • Receptors, Pituitary Hormone / chemistry
  • Receptors, Pituitary Hormone / physiology*
  • Receptors, Vasoactive Intestinal Peptide / chemistry
  • Receptors, Vasoactive Intestinal Peptide / physiology*
  • Receptors, Vasoactive Intestinal Peptide, Type II
  • Sequence Homology, Amino Acid
  • Vasoactive Intestinal Peptide / pharmacology
  • Xenopus Proteins
  • Xenopus laevis

Substances

  • ADCYAP1 protein, Xenopus
  • Adcyap1 protein, mouse
  • Adcyap1 protein, rat
  • Insulin
  • Neuropeptides
  • Neurotransmitter Agents
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
  • Receptors, Pituitary Hormone
  • Receptors, Vasoactive Intestinal Peptide
  • Receptors, Vasoactive Intestinal Peptide, Type II
  • Xenopus Proteins
  • Vasoactive Intestinal Peptide