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Putative Role of Carbon Monoxide Signaling Pathway in Penile Erectile Function


Taymour Mostafa, MD, Faculty of Medicine, Cairo University, Andrology & Sexology Department, Cairo, Egypt. Tel: +2 0105150297; Fax: +202 23632297; E-mail:


Introduction.  Erectile response depends on nitric oxide (NO) generated by NO synthase (NOS) enzyme of the nerves and vascular endothelium in the cavernous tissue. NO activates soluble guanylate cyclase (sGC), leading to the production of cyclic guanosine monophosphate (cGMP). cGMP activates cGMP-dependent protein kinase that activates Ca2+/ATPase pump that activates Ca2+/K efflux pump extruding Ca2+ across the plasma membrane with consequent smooth muscle cell relaxation. A role similar to that of NOS/NO signaling has been postulated for carbon monoxide (CO) produced in mammals from heme catabolism by heme oxygenase (HO) enzyme.

Aim.  To assess CO signaling pathway for erectile function by reviewing published studies.

Methods.  A systematic review of published studies on this affair based on Pubmed and Medical Subject Heading databases, with search for all concerned articles.

Main Outcome Measures.  Documentation of positive as well as negative criteria of CO/HO signaling focused on penile tissue.

Results.  The concept that HO-derived CO could play a role in mediating erectile function acting in synergism with, or as a potentiator for, NOS/NO signaling pathway is gaining momentum. CO/HO signaling pathway has been shown to partially mediate the actions of oral phosphodiesterase type 5 inhibitors. In addition, it was shown that the use of CO releasing molecules potentiated cavernous cGMP levels. However, increased CO production or release was reported to be associated, in some studies, with vasoconstriction.

Conclusion.  This review sheds a light on the significance of cavernous tissue CO signaling pathway that may pave the way for creation of therapeutic modalities based on this pathway. Abdel Aziz MT, Mostafa T, Atta H, Wassef MA, Fouad HH, Rashed LA, and Sabry D. Putative role of carbon monoxide signaling pathway in penile erectile function. J Sex Med 2009;6:49–60.