Cellular perspective of the erection pathway and mechanism of action of PDE5 inhibitors
- During sexual stimulation signals in the brain cause nitric oxide (NO) to be released in the penis.
- NO is transported into the smooth-muscle cells where it activates the enzyme guanilate cyclase, which produces cGMP (cyclic guanosine monophosphate).
- Increased concentration of cGMP causes the outflow of calcium ions (Ca++) from the cell, resulting in smooth-muscle relaxation.
- Consequently the arteries dilate, inflow of blood into the corpora cavernosa increases and blood accumulates, which results in an erection.
- After ejaculation the enzyme phosphodiesterase type 5 (PDE5) reduces cGMP levels and the penis becomes flaccid.
PDE5 inhibitors (e.g. sildenafil) prevent the reduction of cGMP levels and thus help achieve and maintain an erection.