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 concentration-dependent relaxation of the circular muscle of isolated chicken ileum which is unaffected by atropine or propranolol but abolished by tetrodotoxin (TTX). The aim of this study was to investigate whether purinergic (ATP), nitrergic (NO) and peptidergic (VIP) neurons are implicated in the response to CCK-OP. In preparations prerelaxed with ATP, CCK-OP caused a further relaxation (average 46%). In addition, suramin (a P2 purinoceptor antagonist) inhibited the response to both 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 (to about 10% of the original response). Moreover, in preparations prerelaxed with chVIP, the response to CCK-OP consisted of a small additional relaxation (average 15,7%). The responses to chicken VIP (chVIP) or sodium nitroprusside (NaNP), a NO donor, are TTX resistant whereas that to ATP is blocked by TTX. L-NO-Arg significantly reduced the relaxation induced by ATP, but did not change that induced by chVIP. The response to ATP after exposure of the tissue to maximal chVIP concentration 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 (possibly chVIP). ChVIP and NO interact with receptors located on muscle cells causing the relaxation of the circular muscle coat of the ileum.