Role of ATP and related purine compounds on urethral relaxation in male rabbits.

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Non-adrenergic, non-cholinergic (NANC) relaxation evoked by electrical field stimulation (EFS) has been observed in the urethra, with nitric oxide (NO) considered the agent most probably mediating this effect. However, Burnstock's purinergic hypothesis suggests that ATP and related purine compounds are neurotransmitters in NANC relaxation, although the physiological and pharmacological effects of ATP and related purine compounds in the urethra have been little studied. The effects of ATP and related purine compounds, NG-nitro-L-arginine (NOARG; an inhibitor of nitric oxide synthesis from L-arginine), calcitonin gene-related peptide (CGRP), substance P and vasoactive intestinal polypeptide (VIP) on relaxation and smooth muscle tension induced by electrical field stimulation (EFS) were studied in isolated male rabbit circular urethral smooth muscle (functional study). In addition, the outflow of ATP elicited by EFS was measured using the luciferase technique (superfusion study). All experiments were performed in the presence of guanethidine (3 x 10(-3) mol/L) and atropine (10(-6) mol/L). In preparations contracted with U46619, a prostaglandin peroxidase inhibitor, ATP had almost no effect on EFS-induced relaxation; however, suramin, a non-selective P2Y-purinoceptor antagonist, and NOARG each markedly attenuated this relaxation in a concentration-dependent manner. ATP and related purine compounds (adenosine, AMP and ADP) each reduced U46619-induced tonic contraction in a concentration-dependent manner. The potencies of the relaxant effects of ATP and these purine compounds were almost the same. In preparations contracted with U46619, CGRP and substance P had no effect on tonic contraction, but VIP reduced tonic contraction in a concentration-dependent manner. In the superfusion study, the outflow of ATP into the superfusate was markedly increased by EFS. When NOARG or prazosin was added to the superfusate, the increase in outflow of ATP was unchanged, but when suramin was added to the superfusate, no increase in outflow of ATP was observed. These findings suggest that P2Y-purinoceptors exist in the male rabbit urethra, and that ATP and related purine compounds may play a role in non-adrenergic, non-cholinergic neurotransmission. Consequently, the pathways mediating urethral relaxation by ATP, NO and VIP may be different.