Acetylcholine and the overactive bladder.

Currently, the most widely used and effective pharmacologic treatment for the overactive bladder (OAB) is administration of muscarinic receptor antagonists. This strongly suggests that acetylcholine plays some role in the aetiology of bladder overactivity. If one considers the classical picture of the involvement of acetylcholine in the human bladder, this seems surprising. Acetylcholine is the main transmitter released from the parasympathetic nerves and is responsible for initiating synchronous contraction of the detrusor, resulting in the raised intravesical pressure that accompanies micturition. Urodynamic studies of anaesthetised animals show the effects of antimuscarinic drugs that one might expect, that is, that inhibition of the muscarinic receptors leads to a progressive reduction in voiding efficiency, shown by a reduction of peak pressure, development of residual urine, and an increase in the frequency of micturition. Fig. 1 is from an experiment on anaesthetised guinea pigs carried out in my laboratory by Huw Williams (Derby) recording intravesical pressure and illustrating the effect of intravenous administration of atropine on the micturition cycle. Micturition continued in the presence of atropine (albeit less efficiently) because in these small mammals adenosine triphosphate (ATP) is also a transmitter in the parasympathetic nerves and simultaneous inhibition of the appropriate purinergic receptors abolishes micturition completely. ATP appears to play little role in activating the human