Neuromodulation of penile erection: An overview of the role of neurotransmitters and neuropeptides

Penile erection is regulated by several neurotransmitters and neuropeptides at penile tissue and central nervous system levels. At penile level, the key event is the relaxation of corpora cavernosa smooth muscles. Here, three kinds of neural autonomic control have been characterized in detail, one adrenergic stimulatory, that under normal conditions maintains the corpora cavernosa contracted (that is a flaccid penis), a second cholinergic inhibitory that is believed to cooperate with a third, nonadrenergic-noncholinergic control also inhibitory, possibly mediated by nitric oxide (NO), to reduce the adrenergic tone favouring the relaxation of corpora cavernosa, as during a sexual stimulus. However, the complex interactions between these neurotransmitters that determine the final condition of the corpora cavernosa, e.g. the presence or the absence of penile erection, are still a matter of controversy. This is further complicated by the presence of several neuropeptides in nervous penile vascular and smooth muscle tissues such as vasoactive intestinal polypeptide, peptide histidine-isoleucine, peptide histidine-methionine, neuropeptide Y and endothelins, that often exert very potent (relaxant or contractant) effects in penile tissues. Also at the central level, several neurotransmitters and neuropeptides,that influence penile erection have been identified. Among neurotransmitters, the most studied are dopamine (DA), serotonin (5HT), acetylcholine (ACh), glutamic acid and NO. DA, ACh, glutamic acid and NO seem to have a facilitatory role, while 5HT may be either facilitatory or inhibitory, depending on the receptor subtype involved. Among neuropeptides, the best known are oxytocin, adrenocorticotropin (ACTH)-alpha-melanocyte stimulating hormone (alpha-MSH)-related peptides and opioid peptides. Interestingly DA, glutamic acid and NO seem to facilitate while opioid peptides inhibit penile erection by increasing and decreasing, respectively, central oxytocinergic transmission by acting in the paraventricular nucleus of the hypothalamus. ACTH-MSH peptides also facilitate penile erection, although with a mechanism(s) different from those recalled above. Despite some recent progress, more has still to be done to clarify the role played by neurotransmitters and neuropeptides at peripheral and central levels in the control of this primary sexual function.