NEURAL MODULATION OF THE ANTISECRETORY EFFECT OF PEPTIDE YY IN THE RAT JEJUNUM

The endocrine and neural peptide, peptide YY, inhibits intestinal secr etion of water and electrolytes in several animal species and in man. Peptide YY receptors have been evidenced on isolated rat jejunal crypt cells, but neural receptors are also likely to participate in the ant isecretory effect of peptide YY in vivo. The aim of the present study was to investigate the mechanisms of the peptide YY effect on vasoacti ve intestinal peptide (VIP)-stimulated jejunal net water flux in the r at. Antagonist experiments using several drugs affecting neurally medi ated processes were done for the purpose. A small peptide YY dose (10 pmol/kg) inhibited significantly (P < 0.005) the jejunal net water flu x produced by 30 mu g/kg per h of VIP. The inhibitory effect of peptid e YY was suppressed, or strongly and significantly reduced, by tetrodo toxin, hexamethonium, lidocaine, idazoxan and BMY14,802 5-fluoro-2-pyr imidinyl)-1-piperazinyl)-1-butanol), whereas devazepide and L-NAME (L- omega-N-arginine methyl ester) had no effect. These results suggest th at peptide YY inhibits VIP-stimulated jejunal net water flux in vivo t hrough a neural mechanism implicating the participation of nicotinic s ynapses, alpha(2)-adrenoceptors and sigma receptors. (C) 1997 Elsevier Science B.V.