Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hot water extracts of Mo-er (1 gm by 15 ml of water), an oriental food (Auricularia auricula), inhibit strongly both human and rat platelet ADP-induced aggregation. HPLC analysis of two varieties of Mo-er, A. auricula and A. polytricha (a black tree fungus), shows that they contain adenosine (Ado), 133 and 154 micrograms per gram of dry fungus, respectively. The inhibition of ADP-induced platelet aggregation by Mo-er extracts and by Ado was compared. Mo-er extracts caused a more rapid onset and a longer duration of inhibition that produced by equivalent amounts of Ado. Furthermore, Mo-er extract treated with adenosine deaminase to degrade the Ado retained the capacity to inhibit platelet aggregation. The inhibitory effects of Mo-er extracts of ADP-induced human platelet aggregation are greatly potentiated by the inhibitors of cyclic AMP phosphodiesterase such as oxagrelate (phthalazinol) and papaverine. The inhibition of platelet aggregation is only partially blocked by 2',5'-dideoxy-adenosine (DDA), an inhibitor of platelet adenylate cyclase and 5'-deoxy, 5'-methylthioadenosine (MTA), an antagonist of ADO receptors. ADP-induced rat platelet aggregation is strongly inhibited by Mo-er extracts, but not by Ado. This inhibition is not reversed by either DDA or MTA. These findings indicate that Mo-er extracts contain an agent (or agents) in addition to Ado, that blocks platelet aggregation by a mechanism that does not involve the platelet cyclic AMP system.
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PMID:Inhibition of human and rat platelet aggregation by extracts of Mo-er (Auricularia auricula). 698 40

We hypothesized that pulmonary vasorelaxation mediated by receptors that require generation of cyclic adenosine monophosphate (cAMP) is impaired in endotoxin-induced acute lung injury. The purpose of this study was to determine the effect of endotoxin on the following pathways of pulmonary vasorelaxation that require the generation of cAMP: 1) beta-adrenoreceptor stimulation (response to isoproterenol, ISO), 2) P2 purinoreceptor stimulation (response to adenosine diphosphate, ADP), 3) H2-histamine receptor stimulation (response to dimaprit), 4) adenosine A2 receptor stimulation (response to adenosine, ADO), 5) type 2 E prostaglandin (EP2) receptor stimulation (response to prostaglandin E1, PGE1), and 6) direct adenylate cyclase stimulation (response to forskolin, FSK). We used isolated pulmonary artery rings harvested from rats injected with endotoxin or saline. We found that endotoxin impaired the response to beta-adrenoreceptor stimulation (ISO) and P2 purinoreceptor stimulation (ADP). Endotoxin converted the vasorelaxant effect of H2-histamine receptor stimulation (dimaprit) to vasoconstriction. On the other hand, the response to A2 receptor stimulation (ADO) and EP2 receptor stimulation (PGE1), was normal. The dose response to direct adenylate cyclase stimulation (FSK) was the same as control except at a single concentration (10(-7) M). These data suggest that endotoxin causes selective impairment of pulmonary vasorelaxation through receptors coupled to cAMP generation. This impaired pulmonary vasorelaxation may contribute to the increased pulmonary vascular resistance seen in acute lung injury. These data may lead to therapy that will prevent or improve the pathophysiologic pulmonary circulation in acute lung injury.
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PMID:Selective inhibition of receptor-mediated pulmonary vasorelaxation in endotoxin-induced acute lung injury. 898 34