Evidence of Adenosine 5′-Triphosphate Release From Nerve and P2x-Purinoceptor Mediated Contraction During Electrical Stimulation of Rat Urinary Bladder Smooth Muscle

PURPOSE: We provided direct evidence for the existence of purinergic innervation in the rat urinary bladder. MATERIALS AND METHODS: The non-adrenergic non-cholinergic (NANC) innervation was studied in 4-month-old Wistar rats. Electric-field stimulation (EFS) of the detrusor muscle strips in the presence of four autonomic blockers (atropine 10(-6) M, guanethidine 10(-6) M, phentolamine 10(-6) M and propranolol 10(-6) M) showed NANC contractions accounted for about 50% of the maximum contractile response. The adenyl purines released from nerves by EFS were detected by HPLC after conversion to ethenopurines. The amount of total purine released was frequency-dependent and could be totally suppressed by tetradotoxin (10(-6) M). The amount of ATP released was significantly greater than those for ADP, AMP and adenosine (p < 0.05, n = 4). Desensitization induced by alpha, beta-MeATP (10(-6) to 10(-4) M), a P2x receptor agonist, reduced the NANC contraction. In addition, the NANC contraction was also abolished by P2 receptor blocker suramin (10(-4) to 10(-3) M) and P2x receptor blocker PPADS (10(-5) to 10(-4) M.). CONCLUSION: The results of the present study give evidence to support purinergic nerve-mediated bladder smooth muscle contractions in the rat. Among the purine nucleotides, ATP is the dominant purinergic neurotransmitter released and P2x receptor activation is responsible for the NANC contractile response.