title: Divergent molecular mechanisms underlay CO- and CORM-2-induced relaxation of corpora cavernosa.
abstract: BACKGROUND
  Similar to nitric oxide (NO), the principal mediator of penile erection, carbon monoxide (CO) possesses vasodilator capacities. However, whether CO could be a therapeutic target for treating erectile dysfunction (ED) is unexplored. The danger associated with systemic administration of CO has led to the development of CO-releasing molecules (CORMs), releasing CO in a local, safe and controlled way. These CORMs have shown positive outcomes in cardiovascular studies. More knowledge on the (patho)physiological functions of CO in erectile function and the potential therapeutic role of CORMs is required.
  
  
  OBJECTIVE
  The present study aims the assessment of the effect of CO and CO donor CORM-2 on the corporal tension and the underlying molecular mechanisms.
  
  
  METHODS
  Organ bath studies were performed measuring isometric tension on isolated mice corpora cavernosa (CC) strips. Responses to CO (10-300 µmol/L) and CORM-2 (10-100 µmol/L) were measured in the presence/absence of activators/inhibitors of different molecular pathways.
  
  
  METHODS
  CO and CORM-2 relax corporal strips concentration dependently, although the molecular mechanisms behind the corporal relaxation seem to differ completely.
  
  
  RESULTS
  CO induces corporal relaxation by activating soluble guanylyl cyclase (sGC), increasing cyclic guanosine monophosphate (cGMP) concentrations. The molecular mechanism involved in CORM-2-induced corporal relaxation is not related to sGC activation and remains obscure.
  
  
  CONCLUSIONS
  Both CO and CORM-2 induce corporal relaxation, although the underlying molecular mechanisms show no resemblance. That CO induces corporal relaxation through a mechanism similar to that of NO could be of importance as it indirectly offers the possibility that endogenous CO might serve as a backup system for insufficient NO availability in cases of ED. Whether CORM-2 possesses the same capacity remains questionable and requires further research.
authors: Department of Pharmacology, Ghent University, Ghent, Belgium.
authors: Kelly
authors: K
authors: Decaluwé
authors: Bart
authors: B
authors: Pauwels
authors: Charlotte
authors: C
authors: Boydens
authors: Johan
authors: J
authors: Van de Voorde
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology*; D006157:Guanosine Monophosphate / Q000378:metabolism; D006162:Guanylate Cyclase / Q000187:drug effects; D008297:Male; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009942:Organometallic Compounds / Q000494:pharmacology*; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects; D000071756:Soluble Guanylyl Cyclase
chemical_list: D009942:Organometallic Compounds; D018160:Receptors, Cytoplasmic and Nuclear; C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide; D006157:Guanosine Monophosphate; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase