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 (V IP) 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 an d guinea pig. VIP1-R and VIP2-R mRNA were identified in dispersed acini fro m both species by Northern blot analysis and in rat by Southern blot analys is. With the use of the VIP2-R-selective ligand Ro-25-1553 in both species, inhibition of binding of I-125-labeled VIP to acini showed a biphasic patt ern with a high-affinity component (10%) and a second representing 90%. The VIP1-R-selective ligand, [Lys(15) ,Arg(16),LeU(27)]VIP-(1- 7)-GRF-(8-27), gave a monophasic pattern. Binding of Ro-25-1553 was better fit by a two-si te model. In both rat and guinea pig acini, the dose-response curve of Re-2 5-1553 for stimulation of enzyme secretion was biphasic, with a high-affini ty component of 10-15% of the maximal secretion and a low-affinity componen t accounting for 85-90%. At low concentrations (10 nM) of Ro-25-1553 and [L ys(15),Arg(16),Leu(27)]VIP-(1-7)-GRF(8-27), which only occupy VIP receptors , a 4-fold and a 56-fold increase in cAMP occurred, respectively. These res ults 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 subty pes, which will need to be considered in future studies of the action of VI P in the pancreas.