FUNCTIONAL IMPORTANCE OF CHOLINERGIC AND PURINERGIC NEUROTRANSMISSIONFOR MICTURITION CONTRACTION IN THE NORMAL, UNANESTHETIZED RAT

1 The cholinergic and purinergic neurotransmission involved in micturi tion in the normal, unanaesthetized rat was investigated by means of c ontinuous cystometry. 2 ATP (1 and 5 mg kg-1), administered intra-arte rially (i.a.) close to the bladder, produced rapid, phasic, dose-depen dent increases in bladder pressure with micturition immediately after injection. The micturition pressure of the following spontaneous voidi ngs increased, and bladder capacity, micturition volume, and residual volume decreased. Pretreatment with alpha,beta-methylene ATP (I mg kg- 1, i.a.) blocked the effects of ATP (5 mg kg-1). 3 alpha,beta-Methylen e ATP (0.25, 0.5 and 1 mg kg-1, i.a.) produced rapid, phasic, increase s in bladder pressure with micturition immediately after injection. Th e effects of alpha,beta-methylene ATP (0.25 mg kg-1, i.a.) were not af fected by pretreatment with indomethacin (0.5-2 mg kg-1, i.a.). The mi cturition pressure of the subsequent spontaneous voidings decreased, a nd bladder capacity and residual volume increased. 4 Carbachol (5-50 m ug kg-1, i.a.) produced rapid, sustained, dose-dependent increases in bladder pressure with micturition, and then increased basal pressure, threshold pressure, and micturition pressure, and decreased bladder ca pacity and micturition volume during the following spontaneous voiding s. 5 Atropine (1 mg kg-1, i.a.) decreased micturition pressure and mic turition volume, but did not induce dribbling incontinence. Micturitio n contractions still occurred after the injection, but changed in appe arance and were of shorter duration than before. In the presence of at ropine (I mg kg-1, i.a.), alpha,beta-methylene ATP (1 mg kg-1, i.a.) p roduced initially a phasic increase in bladder pressure with micturiti on and then dribbling incontinence in all animals tested. 6 After bloc kade of the micturition reflex with morphine (10 mug intrathecally), A TP (5 mg kg-1, i.a.), alpha,beta-methylene ATP (0.25-1 mg kg-1, i.a.), and carbachol (5-500 mug kg-1, i.a.) were unable to empty the bladder . 7 The results suggest that drug-induced bladder emptying in the norm al, unanaesthetized rat requires an intact micturition reflex and they support the view that the two physiologically important transmitters involved in micturition are acetylcholine and ATP.