Purinergic sensory neurotransmission in the urinary bladder: an in vitro study in the rat

Objectives To determine the response of mechanosensitive pelvic nerve affer ents, arising from the rat urinary bladder, to the purinergic agonist alpha ,beta-methylene ATP and to the purinergic antagonist suramin. Materials and methods Using a newly developed in vitro bladder-pelvic nerve afferent model, multiunit recordings were taken from mechanosensitive pelv ic nerve afferents arising from the rat urinary bladder, in response to bla dder distension, Control experiments were performed by distending the bladd er with saline at 0.04 mL/min, and recording the total afferent nerve activ ity and the bladder pressure response to the distension. Bladder distension s were then repeated using a solution of the stable purinergic agonist; alp ha,beta-methylene ATP (10 mu mol/L), which is known to desensitize P2X-puri noceptors after prolonged exposure, and the total afferent activity and bla dder pressure response were again measured. In a separate series of experim ents the afferent nerve activity and bladder pressure response to bladder d istension with saline was determined in the presence of the purinergic anta gonist suramin (10 mu mol/L) and repeated after washout of the drug. In bot h series of experiments, afferent nerve responses were compared with contro l using the paired t-test, whilst the bladder pressure responses were compa red using one-way analysis of variance. Results Bladder distension with alpha,beta-methylene-ATP produced a statist ically significant reduction in afferent nerve activity, by up to 75% compa red with the control, whilst having no significant effect on the bladder pr essure response. Bladder distension with saline in the presence of suramin (10 mu mol/L) produced a significant reduction in the resultant afferent ne rve activity, by 50%, which returned to normal after washout of the drug. Conclusion These findings are consistent with the notion that ATP is releas ed endogenously during bladder distension in the rat and is involved signif icantly in the activation of pelvic nerve afferents arising from the fat ur inary bladder.