Putative role of carbon monoxide signaling pathway in penile erectile function.
BACKGROUND
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 Ca(2+)/ATPase pump that activates Ca(2+)/K efflux pump extruding Ca(2+) 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.


OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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
Mohamed T
MT
Medical Biochemistry, Unit of Molecular Biology, Cairo University, Cairo, Egypt.
Mostafa
Taymour
T
Atta
Hazem
H
Wassef
Mohamed A
MA
Fouad
Hanan H
HH
Rashed
Laila A
LA
Sabry
Dina
D
D000252:Calcium-Transporting ATPases / Q000502:physiology; D002248:Carbon Monoxide / Q000502:physiology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology; D007172:Erectile Dysfunction / Q000378:metabolism* / Q000503:physiopathology*; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology; D006801:Humans; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); D017869:Cyclic GMP-Dependent Protein Kinases; D000252:Calcium-Transporting ATPases