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

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.