EVIDENCE SUPPORTING A ROLE FOR ATP AS NONADRENERGIC NONCHOLINERGIC INHIBITORY TRANSMITTER IN THE PORCINE ILEUM

The aim of this study was to investigate the nature of the non-adrener gic non-cholinergic (NANC) inhibitory transmitter of the circular musc le of the porcine ileum. For this purpose, the effects of putative NAN C mediators i.e. NO, vasoactive intestinal polypeptide (VIP) and ATP w ere measured in isolated organ bath experiments (in basal conditions a nd after incubation with neostigmine 3 x 10(-5) M) and using the micro electrode technique. The NO donor sodium nitroprusside (NaNP) up to 10 (-4) M, VIP up to 10(-7) M and ATP up to 10(-4) M failed to cause sign ificant relaxation in the basal state. However, all of them induced ma rked relaxations when the tissue had been preincubated with neostigmin e (3 . 10(-5) M) which was added to increase basal mechanical activity . The resting membrane potential (RMP) was unaffected by NaNP(up to 10 (-4) M and VIP up to 10(-7) M whereas ATP (up to 10(-4) M) induced a t ransient hyperpolarization. The inhibitory juntion potentials (IJPs) i nduced by electrical field stimulation (EFS) were not affected by N om ega-nitro-L-arginine (L-NNA) (10(-4) M) whereas suramin, a purinocepto r antagonist, decreased (10(-4) M) or abolished (10(-3) M) the IJPs. R elaxations induced by ATP in neostigmine preincubated tissue were resi stant to 10(-6) M tetrodotoxin, an axonal blocker, and inhibited by su ramin. Apamin (10(-6) M, a small conductance calcium activated potassi um channel blocker, completely abolished the IJP (n=5) and significant ly decreased the relaxation induced by ATP (n=5). The present data pro vide support to the hypothesis that ATP is the NANC inhibitory transmi tter in the porcine ileum acting on P-2 muscular receptors. Neverthele ss, VIP and NaNP do also cause relaxation of preparations preincubated with neostigmine.