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1 Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and 2 Peptide Research Laboratories, Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112
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-(827),
gave a monophasic pattern. Binding of Ro-25-1553 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-(17)-GRF(827),
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.
vasoactive intestinal peptides; adenosine 3',5'-cyclic monophosphate; pancreatic secretion; vasoactive intestinal peptide receptors
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