ABSTRACT
Neurocrine, endocrine, and paracrine regulators are critical to the control of colonic secretion. These studies have investigated the inhibition of vasoactive intestinal polypeptide (VIP)-stimulated ion transport by peptide YY (PYY) and other Y-class effectors in rabbit distal colonic mucosa mounted in Ussing chambers. PYY decreased basal short-circuit current (Isc) but did not significantly change either basal Na+ or Cl- flux. PYY inhibited VIP-stimulated increases in Isc by up to 86% and abolished VIP-induced Cl- secretion. PYY decreased VIP-generated increases in Isc by a tetrodotoxin-insensitive mechanism. PYY inhibited cholera toxin-stimulated as well as forskolin-stimulated increases in Isc but failed to alter stimulation by 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP). PYY decreased VIP-stimulated increases in tissue cAMP by 88% and forskolin-stimulated increases by 84%. PYY, neuropeptide Y (NPY), (Leu31,Pro34)-NPY, and pancreatic polypeptide (PP) all demonstrated potent inhibition of VIP-stimulated increases in Isc. PYY-(13-36) demonstrated little effect on VIP stimulation. Thus the rabbit distal colon possesses a novel Y-class receptor phenotype that demonstrates high affinity for all three PP-fold peptides, NPY, PYY, and PP.
Subject(s)
Chlorides/metabolism , Colon/physiology , Intestinal Mucosa/physiology , Neuropeptide Y/pharmacology , Peptides/pharmacology , Receptors, Neuropeptide Y/physiology , Sodium/metabolism , Vasoactive Intestinal Peptide/pharmacology , Animals , Biological Transport/drug effects , Colon/drug effects , Cyclic AMP/metabolism , Electric Conductivity/drug effects , Gastrointestinal Hormones/pharmacology , In Vitro Techniques , Intestinal Mucosa/drug effects , Kinetics , Membrane Potentials/drug effects , Pancreatic Polypeptide/pharmacology , Peptide YY , Rabbits , Receptors, Neuropeptide Y/antagonists & inhibitorsABSTRACT
We have studied the effect of neuropeptide Y on basal and vasoactive intestinal polypeptide-stimulated changes in the short-circuit current of strips of colonic mucosa from New Zealand white rabbits mounted in Ussing chambers. When administered to the basolateral surface, neuropeptide Y is found to decrease basal short-circuit current. Neuropeptide Y inhibits vasoactive intestinal peptide-stimulated increases in short-circuit current in a concentration-dependent fashion by a tetrodotoxin-insensitive mechanism. Also, neuropeptide Y inhibited increases in short-circuit current produced by direct stimulation of adenylate cyclase with forskolin. Furthermore, neuropeptide Y prevents vasoactive intestinal peptide-stimulated increases in tissue cyclic adenosine monophosphate levels. These results indicate that neuropeptide Y administered to the basolateral membrane inhibits vasoactive intestinal peptide-stimulated short-circuit current changes by a tetrodotoxin-insensitive mechanism that decreases tissue levels of cyclic adenosine 3',5'-monophosphate.
