PACAP/VIP receptors in pancreatic beta-cells: their roles in insulin secretion.
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.
Inagaki
N
N
Division of Molecular Medicine, Chiba University School of Medicine, Japan.
Kuromi
H
H
Seino
S
S
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D005260:Female; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009865:Oocytes / Q000502:physiology; D009928:Organ Specificity; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000737:chemistry / Q000502:physiology*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000737:chemistry / Q000502:physiology*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D017386:Sequence Homology, Amino Acid; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D029867:Xenopus Proteins; D014982:Xenopus laevis
C495404:ADCYAP1 protein, Xenopus; C495402:Adcyap1 protein, mouse; C495403:Adcyap1 protein, rat; D007328:Insulin; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D029867:Xenopus Proteins; D014660:Vasoactive Intestinal Peptide