Fig. 1

Possible mechanism of mirabegron’s effect, used for overactive bladder treatment, on female sexual function. β3- adrenergic receptor activation by mirabegron agonist is coupled to the generation of the second messenger cGMP, which causes human corporal cavernosum smooth muscle relaxation by lowering intracellular levels of free calcium. β3 receptor-mediated corporal smooth muscle relaxation involves inhibition of RhoA/Rho-kinase [34]. The Rho pathway is initiated by ET-1 agonist binding in the GPCR receptor, which activates RhoGEF, facilitating RhoA–GDP conversion to RhoA–GTP. RhoA–GTP binds to ROCK, facilitating autophosphorylation of ROCK that enhances its ability to phosphorylate and deactivate MLCP, promoting vasoconstriction. Relaxation is largely mediated by cGMP, which causes phosphorylation of RhoA, preventing interaction with ROCK and thereby inhibiting vasoconstriction. Endothelin-1-induced contraction of corporal smooth is mediated by an up-regulation of Rho kinase-β protein in alloxan-induced diabetic human corpus cavernosum [36]. Internal pudendal artery and clitoral artery are sensitive to the potent vasoconstrictor peptide, endothelin-1 (ET-1). The inhibition of Rho-kinase in the internal pudendal artery and clitoral artery reduces ET-1-mediated constriction [39].m. Abr. cGMP: cyclic GMP, GPCR: G-protein-coupled receptor, MLCP: myosin light chain phosphatase, RhoGEF: Rho guanine exchange factor, ROCK: Rho-associated protein kinase, sGC: soluble guanylyl cyclase, Y-27632: (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide, ET-1: Endothelin-1