Decreased Ecto-Ntpdase1/Cd39 Activity Leads to Desensitization of P2 Purinoceptors Regulating Tonus of Corpora Cavernosa in Impotent Men with Endothelial Dysfunction

Abstract

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.

Keywords:

• Erectile dysfunction
• human corpus cavernosum
• P2 purinoceptors
• ectonucleotidases
• ecto-NTPDase1/CD39
• adenine nucleotides

This work was supported by FCT (FEDER Funding, POCTI/FCB/45549/2002 and SFRH/BD/25470/2005) and Sociedade Portuguesa de Andrologia (SPA).

Notes

∗P < 0.05 as compared with data obtained in control individuals.