INHIBITION OF VIP-STIMULATED ION-TRANSPORT BY A NOVEL Y-RECEPTOR PHENOTYPE IN RABBIT DISTAL COLON

Neurocrine, endocrine, and paracrine regulators are critical to the co ntrol of colonic secretion. These studies have investigated the inhibi tion of vasoactive intestinal polypeptide (VIP)-stimulated ion transpo rt by peptide YY (PYY) and other Y-class effectors in rabbit distal co lonic mucosa mounted in Ussing chambers. PYY decreased basal short-cir cuit current (I(sc) but did not significantly change either basal Naor Cl- flux. PYY inhibited VIP-stimulated increases in I(sc) by up to 86% and abolished VIP-induced Cl- secretion. PYY decreased VIP-generat ed increases in I(sc) by a tetrodotoxin-insensitive mechanism. PYY inh ibited cholera toxin-stimulated as well as forskolin-stimulated increa ses in I(sc) but failed to alter stimulation by 8-bromoadenosine 3',5' -cyclic monophosphate (8-BrcAMP). PYY decreased VIP-stimulated increas es in tissue cAMP by 88% and forskolin-stimulated increases by 84%. PY Y, neuropeptide Y (NPY), (Leu31, Pro34)-NPY, and pancreatic polypeptid e (PP) all demonstrated potent inhibition of VIP-stimulated increases in I(sc). PYY-(13-36) demonstrated little effect on VIP stimulation. T hus the rabbit distal colon possesses a novel Y-class receptor phenoty pe that demonstrates high affinity for all three PP-fold peptides, NPY , PYY, and PP.