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

The effects of purinoceptor ligands for P2X 1 and/or P2X 3 receptors ( α , β‐ meATP, IP 5 I, TNP‐ATP, MRS 2179, PPADS, Phenol red and RO116‐6446/008; 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.α , β‐ meATP (180 nmol kg −1 min −1 ), IP 5 I (10, 30 and 100 nmol kg −1 ), TNP‐ATP (1 μ mol kg −1 ), MRS 2179 (1 μ mol kg −1 ) and PPADS (17 μ mol kg −1 ) each caused maintained bladder contractions to occur during the infusion of saline into the bladder. PPADS (17 μ mol 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 IP 5 I, TNP‐ATP, MRS 2179 and PPADS, the magnitude of postinfusion isovolumetric contractions was significantly reduced and, for IP 5 I, 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. Phenol red (a P2X 1 /P2X 3 antagonist; 0.1 and 1 μ mol 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. RO116‐6446/008 (a P2X 1 ‐selective antagonist; 1 and 10 μ mol kg −1 ) only caused a reduction in postinfusion isovolumetric contractions. It is concluded that P2X 1 and P2X 3 receptors play a fundamental role in the micturition reflex in urethane‐anesthetized female rats. P2X 3 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.British Journal of Pharmacology (2004) 142 , 519–530. doi: 10.1038/sj.bjp.0705790