CONTRIBUTION OF INHIBITORY NEUROTRANSMITTERS TO THE CCK INDUCED RELAXATION OF THE CIRCULAR MUSCLE OF AVIAN ILEUM

The sulphated form of cholecystokinin-octapeptide (CCK-OP) induces a c oncentration-dependent relaxation of the circular muscle of isolated c hicken ileum which is unaffected by atropine or propranolol but abolis hed by tetrodotoxin (TTX). The aim of this study was to investigate wh ether purinergic (ATP), nitrergic (NO) and peptidergic (VIP) neurons a re implicated in the response to CCK-OP. In preparations prerelaxed wi th ATP, CCK-OP caused a further relaxation (average 46 %). In addition , suramin (a P-2 purinoceptor antagonist) inhibited the response to bo th ATP and CCK-OP. L-N-G-nitroarginine (L-NO-Arg) reduced the response to CCK-OP, an effect which was reversed by L-arginine (L-Arg). In the presence of trypsin, the response to CCK-OP was markedly decreased (t o about 10% of the original response). Moreover, in preparations prere laxed with chVIP, the response to CCK-OP consisted of a small addition al relaxation (average 15.7 %). The responses to chicken VIP (chVIP) o r sodium nitroprusside (NaNP), a NO donor, are TTX resistant whereas t hat to ATP is blocked by TTX. C-NO-Arg significantly reduced the relax ation induced by ATP, but did not change that induced by chVIP. The re sponse to ATP after exposure of the tissue to maximal chVIP concentrat ion was significantly reduced (average 25 %). Our results suggest that the effects of CCK-OP seem to be mediated through purinergic neurons, which in turn would stimulate the release of NO and a peptide (possib ly chVIP). ChVIP and NO interact with receptors located on muscle cell s causing the relaxation of the circular muscle coat of the ileum.