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 i nnervation in the rat urinary bladder. Materials and Methods: The non- adrenergic non-cholinergic (NANC) innervation was studied in 4-month-o ld Wistar rats. Electric-field stimulation (EFS) of the detrusor muscl e 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 con tractile response. The adenyl purines released from nerves by EFS were detected by HPLC after conversion to ethenopurines. The amount of tot al purine released was frequency-dependent and could be totally suppre ssed by tetradotoxin (10(-6) M). The amount of ATP released was signif icantly 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 suppor t purinergic nerve-mediated bladder smooth muscle contractions in the rat. Among the purine nucleotides, ATP is the dominant purinergic neur otransmitter released and P2x receptor activation is responsible for t he NANC contractile response.