Receptors for peptide YY and neuropeptide Y on guinea pig pancreatic acini

We examined the effects of peptide YY (PYY), neuropeptide Y (NPY), and their analogues on dispersed pancreatic acini. Binding of [125I]PYY to acini was saturable, reversible, and specific, and PYY binding was best fit with a two-site model. The relative potencies for inhibiting [125I]PYY binding were PYY > or = NPY > NPY(13-36). There was no inhibition of binding with [Leu31,Pro34]NPY, PYX-2, or pancreatic polypeptide. Both PYY and NPY (0.1 microM) inhibited amylase release stimulated by vasoactive intestinal polypeptide (VIP) (0.3 nM) and forskolin (1 microM) by about 30%, but not that stimulated by cholecystokinin-8 or bombesin. The relative potencies for inhibiting VIP-stimulated amylase release were PYY > or = NPY > NPY(13-36), the same as those for inhibiting VIP-stimulated cAMP increase in acini. No inhibition was detected with [Leu31,Pro34]NPY. This work demonstrates Y2 receptors on guinea pig pancreatic acini mediating inhibitory actions of PYY and NPY on pancreatic enzyme secretion.