ALTERATIONS IN CHOLINERGIC AND PURINERGIC SIGNALING IN A MODEL OF THE OBSTRUCTED BLADDER

Abstract

There is increasing evidence that purinergic signaling may have a role in the generation of detrusor contractions in the pathologically unstable human bladder. However, study of the rabbit model of partial bladder outlet obstruction showed a loss in cholinergic and purinergic innervation after 3 months. We examined changes in the cholinergic and purinergic components contributing to nerve mediated detrusor contraction in a rabbit model of detrusor instability secondary to bladder outlet obstruction during the early hypertrophic stage. Partial bladder outlet obstruction was surgically induced in adult male rabbits. At 3 weeks detrusor strips were obtained and contractions were produced by electrical field stimulation in the presence of 1 μM. atropine and/or 30 μM. of the P2-purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2′4′-disulfonic acid, and after adding 1 μM. tetrodotoxin. Purinergic and cholinergic components were calculated and compared with those from sham operated controls. The cholinergic or atropine sensitive component was frequency dependent, that is smaller at lower frequencies. The cholinergic component was decreased in the early obstructed bladder. The pyridoxalphosphate-6-azophenyl-2′4′-disulfonic acid sensitive purinergic component was frequency dependent, that is larger at lower frequencies. The purinergic component was increased in the early obstructed bladder. The overall electrical field stimulation response or the response to KCl was unaltered in the obstructed group. There was no difference in the response in strips from the bladder neck and dome. The purinergic component of nerve mediated detrusor contraction is increased and the cholinergic component is decreased in early stages of bladder obstruction in this rabbit model.