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.
Subject(s)
Antigens, CD/metabolism , Apyrase/metabolism , Endothelium/physiopathology , Impotence, Vasculogenic/physiopathology , Muscle Tonus/physiology , Penis/blood supply , Penis/physiopathology , Receptors, Purinergic P2/metabolism , Adenosine A2 Receptor Agonists , Adenosine Triphosphate/analogs & derivatives , Adenosine Triphosphate/metabolism , Adenosine Triphosphate/pharmacology , Adolescent , Adult , Case-Control Studies , Dose-Response Relationship, Drug , Endothelium/blood supply , Endothelium/enzymology , Endothelium/metabolism , Humans , Impotence, Vasculogenic/enzymology , Impotence, Vasculogenic/metabolism , Male , Middle Aged , Muscle Contraction/drug effects , Muscle Tonus/drug effects , Penis/drug effects , Penis/metabolism , Receptor, Adenosine A2B/metabolism , Signal Transduction/drug effectsABSTRACT
An ethanolic extract of the leaves of Annona muricata was shown to be toxic to adult forms of the snail Biomphalaria glabrata (LC50 9.32 microg mL(-1)) and to larvae of the brine shrimp Artemia salina (LC50 0.49 microg mL(-1)). Activity-guided fractionation of the extract gave rise to a sample with high molluscicidal activity that contained the acetogenins, annonacin (90%), isoannonacin (6%) and goniothalamicin (4%).