Investigation of the effects of P2 purinoceptor ligands on the micturition reflex in female urethane-anaesthetized rats

1 The effects of purinoceptor ligands for P2X(1) and/or P2X(3) receptors (alpha,beta-meATP, IP5I, TNP-ATP, MRS 2179, PPADS, Phenol red and ROI 16-6446/008; i.v., n = 4-5) and for P2Y(1) receptors (PPADS, MRS 2179 and MRS 2269; i.v., n = 3-5) were investigated on the distension-evoked micturition reflex' in the urethane-anaesthetized female rat. 2 alpha,beta-meATP (180 nmol kg(-1)min(-1)), IP5I (10, 30 and 100 nmol kg(-1)), TNP-ATP (1 mumol kg(-1)), MRS 2179 (1 mumol kg(-1)) and PPADS (17 mumol kg(-1)) each caused maintained bladder contractions to occur during the infusion of saline into the bladder. PPADS (17 mumol kg(-1) min-(1)) had a similar effect when infused intravesicularly. Regular bladder contractions were not observed until the infusion of saline was halted. For IP5I, TNP-ATP, MRS 2179 and PPADS, the magnitude of postinfusion isovolumetric contractions was significantly reduced and, for IP5I, this action was also associated with a significant reduction in urethral relaxation. Additionally, TNP-ATP caused a significant increase in the pressure and Volume thresholds required to initiate a reflex. 3 Phenol red (a P2X(1)/P2X(3) antagonist; 0.1 and 1 mumol kg(-1)) caused a significant increase in the pressure and volume thresholds required to initiate a reflex and, at the higher dose, also caused a reduction in postinfusion isovolumetric contractions. 4 RO116-6446/008 (a P2X(1)-selective antagonist; 1 and 10 mumol kg(-1)) only caused a reduction in postinfusion isovolumetric contractions. 5 It is concluded that P2X(1) and P2X(3) receptors play a fundamental role in the micturition reflex in urethane-anesthetized female rats. P2X3 receptor blockade raised the pressure and volume thresholds for the reflex, whereas P2X(1) receptor blockade diminished motor activity associated with voiding. P2Y(1) receptors may be involved in inhibition of rat detrusor tone.