Neurotransmission and the contraction and relaxation of penile erectile tissues

The balance between contractant and relaxant factors controls the smooth muscle of the corpus cavernosum and determines the functional state of the penis (detumescence and flaccidity versus tumescence and erection). Noradrenaline contracts both the corpus cavernosum and penile vessels, mainly via stimulation of alpha(1)-adrenoceptors. Recent investigations have demonstrated the presence of several subtypes of alpha 1-adrenoceptors (alpha(1A), alpha(1B), and alpha(1D)) in the human corpus cavernosum and also that the noradrenaline-induced contraction in this tissue is probably mediated by two or, possibly, three receptor subtypes. Even if much of the available in vitro information suggests that endothelins (ETs) may be of importance for mechanisms of detumescence and flaccidity, the role of the peptides in the control of penile smooth-muscle tone in vivo is unclear, as is the question as to whether they can contribute to erectile dysfunction. For further evaluation of the clinical importance of ETs in penile physiology and pathophysiology, clinical studies on ET-receptor antagonists would be of interest. Neurogenic nitric oxide (NO) has been considered the most important factor for relaxation of penile vessels and the corpus cavernosum, but recent studies in mice lacking neurogenic NO synthase (NOS) have shown these animals to have normal erections. This focuses interest on the role of endothelial NOS and on other agents released from nerves or endothelium. For the time being the most effective means of inducing penile erection in men involves the intracavernous administration of prostaglandin E1 (PGE1). PGE1 may act partly by increasing intracellular concentrations of cyclic adenosine monophosphate (cAMP). Recent results obtained with the adenylate cyclase stimulator forskolin suggest that penile smooth-muscle relaxation leading to penile erection can be achieved through the cAMP pathway. Thus, transmitters and agents acting through this second-messenger system may significantly contribute to relaxation of penile smooth muscle and to erection.