Functional importance of cholinergic and purinergic neurotransmission for micturition contraction in the normal, unanaesthetized rat.

1. The cholinergic and purinergic neurotransmission involved in micturition in the normal, unanaesthetized rat was investigated by means of continuous cystometry. 2. ATP (1 and 5 mg kg-1), administered intra-arterially (i.a.) close to the bladder, produced rapid, phasic, dose-dependent increases in bladder pressure with micturition immediately after injection. The micturition pressure of the following spontaneous voidings increased, and bladder capacity, micturition volume, and residual volume decreased. Pretreatment with alpha,beta-methylene ATP (1 mg kg-1, i.a.) blocked the effects of ATP (5 mg kg-1). 3. alpha,beta-Methylene ATP (0.25, 0.5 and 1 mg kg-1, i.a.) produced rapid, phasic, increases in bladder pressure with micturition immediately after injection. The effects of alpha,beta-methylene ATP (0.25 mg kg-1, i.a.) were not affected by pretreatment with indomethacin (0.5-2 mg kg-1, i.a.). The micturition pressure of the subsequent spontaneous voidings decreased, and bladder capacity and residual volume increased. 4. Carbachol (5-50 micrograms 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 capacity and micturition volume during the following spontaneous voidings. 5. Atropine (1 mg kg-1, i.a.) decreased micturition pressure and micturition volume, but did not induce dribbling incontinence. Micturition contractions still occurred after the injection, but changed in appearance and were of shorter duration than before. In the presence of atropine (1 mg kg-1, i.a.), alpha,beta-methylene ATP (1 mg kg-1, i.a.) produced initially a phasic increase in bladder pressure with micturition and then dribbling incontinence in all animals tested. 6. After blockade of the micturition reflex with morphine (10 microg intrathecally), ATP (5 mg kg-1, i.a.),alpha,beta-methylene ATP (0.25-1 mg kg-1 , i.a.), and carbachol (5-500 microg kg-1, i.a.) were unable to empty the bladder.7. The results suggest that drug-induced bladder emptying in the normal, 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.