Mode of action of ATP on propulsive activity in rabbit colon

ATP induced a concentration-dependent reduction of the velocity of propulsion in isolated segments of rabbit colon as assessed by the aboral displacement of an intraluminal rubber balloon, and delayed the onset of the propulsive wave. ATP depressed both the reflex contraction of the circular coat above the distended balloon and the response of the circular muscle to transmural (cholinergic) stimulation. On the contrary, ATP (up to 200 muM), while causing relaxation of the circular muscle, had no effect on either the muscular contractile response induced by carbachol and histamine or the non-adrenergic inhibitory responses elicited by electrical stimulation and by radial distension of the gut wall. Within the concentration range used (10-200 muM), ATP concentration-depression curves for propulsion and transmural excitatory stimulation were shifted to the right in the presence of theophylline (10 muM). Theophylline, however, had no influence on either the direct inhibitory action of ATP on circular smooth muscle or the non-adrenergic relaxation in response to electrical stimulation. These data are consistent with the concept that at least two populations of purinergic receptors are present in intestinal tissue. Those populations located presynaptically, unlike those located postsynaptically, are blocked by theophylline. Since the contractile machinery does not appear to be affected by ATP concentrations up to 200 muM, the mechanism by which ATP impairs propulsive activity is probably dependent on activation of presynaptic purinergic receptors located on the nervous pathways subserving the wave of contraction, without having any appreciable influence on descending inhibition.