EVIDENCE FOR PURINERGIC NEUROTRANSMISSION IN THE URINARY-BLADDER OF PITHED RATS

The purpose of this study was to investigate the contribution of adeno sine-5'-triphosphate (ATP) to segmental (L6-S2) spinal electrical stim ulation evoked increases in intra-vesical pressure in pithed rats. Exo genous ATP and substance P produced dose-dependent increases in intra- vesical pressure (ED10 (mmHg) dose required to elicit 10 mmHg increase in intra-vesical pressure) = 1.7 mg/kg and 1.1 mu g/kg, i.v., respect ively). Desensitisation (or antagonism) of P-2x purinoceptors with alp ha, beta-methylene ATP alpha, beta-meATP; 30 mu g/kg per min, i.v.) or pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 10 mg/kg , i.v.) significantly (p < 0.05) antagonized the intra-vesical pressur e responses to ATP (> 8 and 3.6-fold increase in ED10 mmHg, respective ly) but had no significant effect on intra-vesical pressure responses to substance P. Spinal stimulation evoked frequency-dependent increase s in intra-vesical pressure (EF20 (mmHg) frequency required to produce 20 mmHg increase in intra-vesical pressure)= 3.4 Hz). Blockade of mus carinic cholinoceptors and adrenoceptors with atropine (3 mg/kg, i.v.) , propranolol (3 mg/kg, i.v.) and phentolamine (10 mg/kg, i.v.) produc ed marginal attenuation of the intra-vesical pressure responses to spi nal stimulation indicating a major non-adrenergic non-cholinergic (NAN C) component in the overall response. The NANC responses were signific antly (p < 0.05) antagonized by alpha, beta-meATP (30 mu g/kg per min, i.v.) and PPADS (10 mg/kg, i.v.) (> 2.6-fold increase in EF20 (mmHg)) , consistent with involvement of a purinergic neurotransmitter, presum ably ATP. Comparative studies in young (4-6 months) and old (21-23 mon ths) Fischer rats revealed no age-dependent changes in the relative co ntribution of the cholinergic and purinergic systems, with the latter being the dominant one. These findings suggest that purinergic neurotr ansmission, presumably mediated by ATP acting via P,, purinoceptors, r epresents a major component of excitatory innervation to the urinary b ladder in pithed rats. (C) 1998 Elsevier Science B.V. All rights reser ved.