Objectives: To determine the response of mechanosensitive pelvic nerve afferents, 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 pelvic nerve afferents arising from the rat urinary bladder, in response to bladder distension. Control experiments were performed by distending the bladder with saline at 0.04 mL/min, and recording the total afferent nerve activity and the bladder pressure response to the distension. Bladder distensions were then repeated using a solution of the stable purinergic agonist alpha,beta-methylene ATP (10 micromol/L), which is known to desensitize P2X-purinoceptors after prolonged exposure, and the total afferent activity and bladder pressure response were again measured. In a separate series of experiments the afferent nerve activity and bladder pressure response to bladder distension with saline was determined in the presence of the purinergic antagonist suramin (10 micromol/L) and repeated after washout of the drug. In both series of experiments, afferent nerve responses were compared with control using the paired t-test, whilst the bladder pressure responses were compared using one-way analysis of variance.
Results: Bladder distension with alpha,beta-methylene-ATP produced a statistically significant reduction in afferent nerve activity, by up to 75% compared with the control, whilst having no significant effect on the bladder pressure response. Bladder distension with saline in the presence of suramin (10 micromol/L) produced a significant reduction in the resultant afferent nerve activity, by 50%, which returned to normal after washout of the drug.
Conclusion: These findings are consistent with the notion that ATP is released endogenously during bladder distension in the rat and is involved significantly in the activation of pelvic nerve afferents arising from the rat urinary bladder.