Involvement of a purinergic pathway in the sympathetic regulation of motility in rat ileum

We investigated extrinsic neuronal regulation of intestinal motility. The mesenteric nerve stimulation (MNS; duration 0.5 ms, 10 Hz for 30 s) evoked relaxation in the longitudinal muscle direction of the isolated rat ileum. The MNS-induced relaxation was abolished by guanethidine (2 μM) or propranolol (10 μM), but was not affected by prazosin (10 μM), rauwolscine (10 μM), hexamethonium (100 μM) or capsaicin (1 μM). Exposure to a high concentration (100 μM) of ATP (ATP-desensitization) or ADP (ADP-desensitization) reduced the MNS-induced relaxation to 44.7% or 32.5% of the control (P<0.01), respectively. P2 purinoceptor antagonists [suramin (100 μM) and reactive blue-2 (RB-2, 50 μM)] or small conductance Ca²⁺-activated K⁺ channel blocker, apamin (0.5 μM), significantly decreased the relaxation to 54.4% and 25.6% or 19.4% of the control (P<0.01), respectively, whereas selective P2Y₁ purinoceptor antagonist MRS2179 (10 μM) failed to affect the relaxation. Furthermore, exogenous ATP (1 μM) or ADP (1 μM) elicited relaxation in the rat ileum, which was almost abolished by reactive blue-2 (50 μM, 9.1% of control remained, P<0.05). In contrast, relaxation induced by noradrenalin (10 μM) was not antagonized by ATP-desensitization, apamin (0.5 μM) or reactive blue-2 (50 μM). From the present results, we conclude that noradrenergic sympathetic nerves might regulate intestinal motility mediated through a purinergic inhibitory neuronal pathway in the rat small intestine.