Decreased ecto-NTPDase1/CD39 activity leads to desensitization of P2 purinoceptors regulating tonus of corpora cavernosa in impotent men with endothelial dysfunction.
Vascular responses to adenine nucleotides in human corpora cavernosa from men with vasculogenic erectile dysfunction were investigated. We also evaluated the catabolism of extracellular adenine nucleotides to probe its relevance to vascular hemodynamics in impotent men. Human corpora cavernosa have high NTPDase1/CD39 activity, converting ATP directly into AMP, without significant ADP formation. Extracellular ATP hydrolysis is slower in impotent patients. Adenine nucleotides have dual roles on phenylephrine-contracted strips of corpora cavernosa operated by P2X-contractant and P2Y-relaxant receptors. Prolonged exposure to endogenous ATP related to decreased NTPDase1/CD39 activity leads to P2-purinoceptor desensitization in impotent men. Shutting down ATP signaling in vasculogenic impotent men may represent a defense mechanism for preventing purinergic overstimulation.
Faria
M
M
Laboratório de Farmacologia e Neurobiologia/UMIB, Instituto de Ciências Biomédicas Abel Salazar-Universidade do Porto (ICBAS-UP), Porto, Poturgal.
Magalhães-Cardoso
T
T
Lafuente-de-Carvalho
J-M
JM
Correia-de Sá
P
P
D058908:Adenosine A2 Receptor Agonists; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D001081:Apyrase / Q000378:metabolism*; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D018783:Impotence, Vasculogenic / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology*; D010413:Penis / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D043704:Receptor, Adenosine A2B / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D058908:Adenosine A2 Receptor Agonists; D015703:Antigens, CD; D043704:Receptor, Adenosine A2B; D018048:Receptors, Purinergic P2; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D001081:Apyrase; C067869:CD39 antigen; C002630:alpha,beta-methyleneadenosine 5'-triphosphate