Cytosolic Ca2+ responses to sub-picomolar and nanomolar PACAP in pancreatic beta-cells are mediated by VPAC2 and PAC1 receptors

Regul Pept. 2004 Dec 15;123(1-3):147-53. doi: 10.1016/j.regpep.2004.03.020.

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) potentiates glucose-induced insulin release and increases cytosolic Ca2+ concentration ([Ca2+]i) in islet beta-cells in a concentration-dependent manner with two peaks at 10(-13) and 10(-9) M. PAC1 receptor (PAC1-R) and VPAC2 receptor (VPAC2-R) are expressed in pancreatic beta-cells and thought to be involved in insulin release. We aimed to determine the receptor types involved in the [Ca2+]i responses to 10(-13) and 10(-9) M PACAP. We measured [Ca2+]i in beta-cells and examined comparative effects of PAC1-R-selective agonist maxadilan, its antagonist M65, VPAC2-R-selective agonist Ro25-1553, and native ligands of PACAP and VIP. In the presence of 8.3 mM glucose, maxadilan, Ro25-1553, PACAP, and VIP at 10(-13) and 10(-9) M all increased [Ca2+]i. PACAP and maxadilan elicited greater effects at 10(-9) M than at 10(-13) M both in the incidence and amplitude of [Ca2+]i responses. For VIP and Ro25-1553, in contrast, the effects at 10(-9) and 10(-13) M were comparable. Furthermore, the amplitude of [Ca2+]i responses to 10(-9) M PACAP, but not 10(-13) M PACAP, was suppressed by M65. The results suggest that VPAC2-R and PAC1-R contribute equally to [Ca2+]i responses to sub-picomolar concentrations of PACAP, while PAC1-R has greater contribution to [Ca2+]i responses to nanomolar concentrations of this peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Signaling / drug effects
  • Cytosol / metabolism
  • Dose-Response Relationship, Drug
  • In Vitro Techniques
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism*
  • Nerve Growth Factors / administration & dosage*
  • Neuropeptides / administration & dosage*
  • Neurotransmitter Agents / administration & dosage*
  • Peptides, Cyclic / pharmacology
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Rats
  • Rats, Wistar
  • Receptors, Cell Surface / agonists
  • Receptors, Cell Surface / drug effects*
  • Receptors, Cell Surface / metabolism*
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
  • Receptors, Vasoactive Intestinal Peptide / agonists
  • Receptors, Vasoactive Intestinal Peptide / drug effects*
  • Receptors, Vasoactive Intestinal Peptide / metabolism*
  • Receptors, Vasoactive Intestinal Peptide, Type II
  • Vasoactive Intestinal Peptide / analogs & derivatives*
  • Vasoactive Intestinal Peptide / pharmacology

Substances

  • Adcyap1 protein, rat
  • Adcyap1r1 protein, rat
  • Insulin
  • Nerve Growth Factors
  • Neuropeptides
  • Neurotransmitter Agents
  • Peptides, Cyclic
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Cell Surface
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
  • Receptors, Vasoactive Intestinal Peptide
  • Receptors, Vasoactive Intestinal Peptide, Type II
  • Ro 25-1553
  • Vipr2 protein, rat
  • Vasoactive Intestinal Peptide
  • Calcium