Detrusor contraction - Focus on muscarinic receptors

Stimulation of muscarinic receptors is a main mechanism for contractile activation of the detrusor from both animals and humans. Muscarinic receptors are coupled to G-proteins, but the signal transduction systems may vary. In general, M-1 , M-3 and M-5 receptors are considered to couple preferentially to G(q/11) , activating phosphoinositide hydrolysis, in turn leading to mobilization of intracellular calcium through inositol trisphosphate generation. M-2 and M-4 receptors couple to pertussis toxin-sensitive G(i/o) , resulting in inhibition of adenylyl cyclase activity. However, in the detrusor smooth muscle, other signalling pathways may be involved. Recent investigations revealed that a main pathway for muscarinic receptor activation of the detrusor may be calcium influx via L-type calcium channels, and increased sensitivity to calcium of the contractile machinery via inhibition of myosin light chain phosphatase through activation of Rho-kinase. The importance of these findings for treatment of voiding dysfunction remains to be established.