Muscarinic acetylcholine receptors in the urinary tract

Muscarinic receptors comprise five cloned subtypes, encoded by five distinct genes, which correspond to pharmacologically defined receptors (M(1)-M(5)). They belong to the family of G-protein-coupled receptors and couple differentially to the G-proteins. Preferentially, the inhibitory muscarinic M(2) and M(4) receptors couple to G(i/o), whereas the excitatory muscarinic M(1), M(3), and M(5) receptors preferentially couple to G(q/11). In general, muscarinic M(1), M(3), and M(5) receptors increase intracellular calcium by mobilizing phosphoinositides that generate inositol 1,4,5-trisphosphate (InsP3) and 1,2-diacylglycerol (DAG), whereas M(2) and M(4) receptors are negatively coupled to adenylyl cyclase. Muscarinic receptors are distributed to all parts of the lower urinary tract. The clinical use of antimuscarinic drugs in the treatment of detrusor overactivity and the overactive bladder syndrome has focused interest on the muscarinic receptors not only of the detrusor, but also of other components of the bladder wall, and these have been widely studied. However, the muscarinic receptors in the urethra, prostate, and ureter, and the effects they mediate in the normal state and in different urinary tract pathologies, have so far not been well characterized. In this review, the expression of and the functional effects mediated by muscarinic receptors in the bladder, urethra, prostate, and ureters, under normal conditions and in different pathologies, are discussed.