Muscarinic receptors of the urinary bladder: Detrusor, urothelial and prejunctional

The parasympathetic nervous system is responsible for maintaining normal bladder function, contracting the bladder smooth muscle (detrusor) and relaxing the bladder outlet during micturition. Contraction of the bladder involves direct contraction via M₃ receptors and an indirect 're-contraction' via M₂-receptors whereby a reduction in adenylate cyclase activity reverses the relaxation induced by β-adrenoceptor stimulation. Muscarinic receptors are also located on the epithelial lining of the bladder (urothelium) where they induce the release of a diffusible factor responsible for inhibiting contraction of the underlying detrusor smooth muscle. The factor remains unidentified but is not nitric oxide, a cyclooxygenase product or adenosine triphosphate. Finally, muscarinic receptors are also located prejunctionally in the bladder on cholinergic and adrenergic nerve terminals, where M₁-receptors facilitate transmitter release and M₂ or M₄-receptors inhibit transmitter release. In pathological states, changes may occur in these receptor systems resulting in bladder dysfunction. Muscarinic receptor antagonists are the main therapeutic agents available for treatment of the overactive bladder, but whether their therapeutic effect involves actions at all three locations (detrusor, prejunctional, urothelial) has yet to be established.