Neuropeptide action on the guinea-pig bladder; a comparison with the effects of field stimulation and ATP

Abstract

A comparison was made between the effects of several neuropeptides and ATP as possible mediators of the non-adrenergic, non-cholinergic excitatory response in detrusor strips from the guinea-pig urinary bladder. Both substance P and vasoactive intestinal polypeptide produced contractions of the guinea-pig bladder, but the form of the atropine-resistant neurogenic excitation was mimicked more precisely by ATP. Neither methionine enkephalin nor leucine enkephalin had a prominent direct action on the smooth muscle (up to 100 microM) and did not significantly modify the cholinergic or non-cholinergic components of the response elicited by field stimulation. A proteolytic enzyme, chymotrypsin (10 U/ml), antagonised the excitatory effect of substance P, but not that of the non-adrenergic, non-cholinergic excitatory response or ATP. The slow excitation elicited by a high concentration of vasoactive intestinal polypeptide (10 microM), in contrast to responses elicited by ATP or field stimulation, was attenuated by preincubation with the structurally related polypeptide PHI, which was itself inactive (up to 10 microM). The present observations argue against a role for the peptides studied as neuromuscular transmitters in the detrusor but do not preclude such a role for ATP.