Rat and guinea pig pancreatic acini possess both VIP1 and VIP2 receptors, which mediate enzyme secretion

T. Ito, W. Hou, T. Katsuno, H. Igarashi, T. K. Pradhan, S. A. Mantey, D. H. Coy, R. T. Jensen

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Pancreatic acini from most species possess vasoactive intestinal peptide (VIP) receptors. Recently, two subtypes of VIP receptors, VIP1-R and VIP2- R, were cloned. Which subtype exists on pancreatic acini or mediates secretion is unclear. To address this, we examined pancreatic acini from both rat and guinea pig. VIP1-R and VIP2-R mRNA were identified in dispersed acini from both species by Northern blot analysis and in rat by Southern blot analysis. With the use of the VIP2-R-selective ligand Ro-25-1553 in both species, inhibition of binding of 125I-labeled VIP to acini showed a biphasic pattern with a high-affinity component (10%) and a second representing 90%. The VIP1-R-selective ligand, [Lys15,Arg16, Leu27]VIP-(1 7)-GRF-(8 - 27), gave a monophasic pattern. Binding of Ro- 251553 was better fit by a two-site model. In both rat and guinea pig acini, the dose-response curve of Ro-25-1553 for stimulation of enzyme secretion was biphasic, with a high-affinity component of 10-15% of the maximal secretion and a low-affinity component accounting for 85-90%. At low concentrations (10 nM) of Ro-25-1553 and [Lys15,Arg16,Leu27]VIP-(1 - 7)GRF(8 - 27), which only occupy VIP receptors, a 4-fold and a 56-fold increase in cAMP occurred, respectively. These results show that both VIP1-R and VIP2-R subtypes exist on pancreatic acini of rat and guinea pig, their activation stimulates enzyme secretion by a cAMP-mediated mechanism, and the effects of VIP are mediated 90% by activation of VIP1-R and 10% by VIP2-R. Because VIP has a high affinity for both VIP-R subtypes, its effect on pancreatic acini is mediated by two receptor subtypes, which will need to be considered in future studies of the action of VIP in the pancreas.

Original languageEnglish
Pages (from-to)G64-G74
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume278
Issue number1 41-1
DOIs
Publication statusPublished - Jan 2000

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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