title: Adenosine actions are preserved in corpus cavernosum from obese and type II diabetic db/db mouse.
abstract: BACKGROUND
  Erectile dysfunction (ED) in diabetes is associated with autonomic neuropathy and endothelial dysfunction. Whereas the nonadrenergic-noncholinergic (NANC)/neurogenic nitric oxide pathway has received great attention in diabetes-associated ED, few studies have addressed sympathetic overactivity.
  
  
  OBJECTIVE
  To test the hypothesis that adenosine-induced inhibition of adrenergic-mediated contractile responses in mouse corpus cavernosum is impaired in the presence of diabetes.
  
  
  METHODS
  The db/db (obesity and type II diabetes caused by a leptin receptor mutation) mouse strain was used as a model of obesity and type II diabetes, and standard procedures were performed to evaluate functional cavernosal responses.
  
  
  METHODS
  Increased cavernosal responses to sympathetic stimulation in db/db mice are not associated with impaired prejunctional actions of adenosine.
  
  
  RESULTS
  Electrical field stimulation (EFS)-, but not phenylephrine (PE)-, induced contractions are enhanced in cavernosal strips from db/db mice in comparison with those from lean littermates. Direct effects of adenosine, 2-chloro-adenosine, A(1) receptor agonist C-8031 (N6 cyclopentyladenosine), and sodium nitroprusside are similar between the strips from lean and db/db mice, whereas relaxant responses to acetylcholine and NANC stimulation are significantly impaired in the cavernosal strips from db/db mice. 5'-Iodotubercidin (adenosine kinase inhibitor) and dipyridamole (inhibitor of adenosine transport), as well as the A(1) agonist C-8031, significantly and similarly inhibit contractions induced by stimulation of adrenergic nerves in the cavernosal strips from lean and db/db mice.
  
  
  CONCLUSIONS
  Results from this study suggest that corpora cavernosa from obese and diabetic db/db mice display altered neural-mediated responses that would favor penile detumescence, i.e., increased contractile response to adrenergic nerve stimulation and decreased relaxant responses upon activation of NANC nerves. However, increased cavernosal responses to adrenergic nerve stimulation are not due to impaired negative modulation of sympathetic neurotransmission by adenosine in this diabetic model.
authors.affiliation: Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil;; Department of Physiology, Medical College of Georgia, Augusta, GA, USA. Electronic address: fcarneiro@mcg.edu.
authors.forename: Fernando Silva
authors.initials: FS
authors.lastname: Carneiro
authors.affiliation: Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil;; Department of Physiology, Medical College of Georgia, Augusta, GA, USA.
authors.forename: Fernanda R C
authors.initials: FRC
authors.lastname: Giachini
authors.affiliation: Department of Physiology, Medical College of Georgia, Augusta, GA, USA.
authors.forename: Victor V
authors.initials: VV
authors.lastname: Lima
authors.affiliation: Department of Physiology, Medical College of Georgia, Augusta, GA, USA.
authors.forename: Zidonia N
authors.initials: ZN
authors.lastname: Carneiro
authors.affiliation: Department of Physiology, Medical College of Georgia, Augusta, GA, USA.
authors.forename: Romulo
authors.initials: R
authors.lastname: Leite
authors.affiliation: Department of Physiology, Medical College of Georgia, Augusta, GA, USA.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Inscho
authors.affiliation: Department of Physiology, Medical College of Georgia, Augusta, GA, USA; Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Rita C
authors.initials: RC
authors.lastname: Tostes
authors.affiliation: Department of Physiology, Medical College of Georgia, Augusta, GA, USA.
authors.forename: R Clinton
authors.initials: RC
authors.lastname: Webb
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000248:Adenosine Kinase / Q000037:antagonists & inhibitors; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D004176:Dipyridamole / Q000494:pharmacology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008820:Mice, Obese; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D010413:Penis / Q000294:innervation* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; C034214:5-iodotubercidin; C058394:2-chloro-N(6)cyclopentyladenosine; D004176:Dipyridamole; D000248:Adenosine Kinase; D000241:Adenosine; D014372:Tubercidin; D000109:Acetylcholine