Non-adrenergic, non-cholinergic control of the urinary bladder

In the urinary, bladder, ATP is an excitatory neuromuscular transmitter, possibly a cotransmitter with acetylcholine from postganglionic parasympathetic nerves, which activates P2X-purinoceptors. The synthesis of prostaglandins is closely linked to the activation of P2X-purinoceptors, and these compounds make a significant contribution to non-cholinergic neurogenic responses. Many neuropeptides, such as NPY, VIP, somatostatin, SP and CGRP, are found in nerves innervating the lower urinary tract, but it is unlikely that any is a neuromuscular transmitter in the detrusor; rather, they may act as potent modulators of sympathetic and parasympathetic transmission. Modulatory actions are shown by GABA par excellence; this compound is also well represented in vesicular neurons and, via activation of GABAA- or GABAB-receptors, can potentiate or inhibit parasympathetic transmission. Although not discussed in depth in this review, the urinary bladder shows extraordinary plasticity in expression of nerves and of their transmitters and receptors under pathophysiological conditions, including pregnancy and ageing as well as disease states. Finally, the accessibility of the urinary bladder and the enormous range of chemoreceptors that it possesses has led to its being used extensively for pharmacological investigations of transmitter and drug receptors and their subclasses.