Different receptors mediating the inhibitory action of exogenous ATP and endogenously released purines on guinea-pig intestinal peristalsis

1 Adenosine 5'-triphosphate (ATP) is an enteric neurotransmitter which acts at purine receptors on intestinal nerve and muscle. This study set out to shed light on the receptor mechanisms by which exogenous and endogenous ATP influences intestinal peristalsis. 2 Peristalsis in isolated segments of the guinea-pig small intestine was tr iggered by a perfusion-induced rise of the intraluminal pressure. Motor cha nges were quantified by alterations of the peristaltic pressure threshold ( PPT) at which propulsive muscle contractions were elicited. 3 ATP (greater than or equal to 3 mu M) increased PPT and abolished perista lsis at concentrations of 100-300 mu M. Adenosine 5'-O-2-thiodiphosphate (A DP beta S, 3-100 mM) was more potent, whereas alpha,beta-methylene ATP (alp ha,beta-meATP, 3-100 mu M) was less potent, than ATP in depressing peristal sis. 4 8-Phenyltheophylline (10 mu M) attenuated the anti-peristaltic effect of 10 and 30 mu M ATP but not that of higher ATP concentrations. Apamin (0.5 m u M) counteracted the ability of ATP, ADP beta S and alpha,beta-meATP to en hance PPT. Suramin (300 mM) and pyridoxal phosphate-6-azophenyl-2',4'-disul phonic acid (PPADS, 150 mu M) antagonized the inhibitory effect of alpha,be ta-meATP on peristalsis but did not alter the effect of ATP and ADP beta S. 5 PPADS (50-150 mu M) reduced PPT by as much as 50%. This stimulant effect on peristalsis was prevented by suramin (300 mu M) but left unaltered by ap amin (0.5 mu M) and N-G-nitro-L-arginine methyl ester (300 mu M). 6 These data show that exogenous and endogenous ATP inhibits intestinal per istalsis via different apamin-sensitive purinoceptor mechanisms. Exogenous ATP depresses peristalsis mostly via suramin- and PPADS-insensitive P2 rece ptors, whereas endogenous purines act via P2 receptors sensitive to both su ramin and PPADS.