a | Upon sexual stimulation, normal erection occurs after nitric oxide (NO) release from non-adrenergic non-cholinergic (NANC) nerve fibres causes the activation of guanylyl cyclase, which raises the concentration of cyclic GMP, and after parasympathetic cholinergic nerve fibres release acetylcholine, which activates adenylyl cyclase to increase the levels of cyclic AMP. Signalling pathways that are triggered decrease intracellular Ca2+ levels and lead to smooth muscle cell relaxation. b | As the smooth muscle relaxes, blood is able to fill the lacunar spaces in the cavernosa, leading to compression of the subtunical venules, thereby blocking the venous outflow. The process is reversed as cGMP is hydrolysed by phosphodiesterase type 5 (PDE5). ER, endoplasmic reticulum; InsP3, inositol trisphosphate; NOS, NO synthase; PtdIns(4,5)P2, phosphatidylinositol 4,5 bisphosphate.