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)

The ability of adenosine to stimulate adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] and increase adenosine 3':5'-cyclic monophosphate (cAMP) levels has important biochemical consequences. These include the suppression of immune responses and cardiovascular effects. Recent investigations involving the ability of adenosine and adenosine analogs to stimulate adenylate cyclase provided experimental data that appear to be correlated with the ability of adenosine and analogs of adenosine to exist in the glycosidic high anti conformation. 9-beta-D-Arabinofuranosyladenine, which is not stable in the high anti conformation, is inactive as a stimulator of adenylate cyclase. 2'-Deoxyadenosine is also not stable in the high anti conformation but its instability may be significantly decreased by intramolecular adjustments promoted by receptor or active site interactions. 2'-Deoxyadenosine does not activate adenylate cyclase in lymphocytes when ATP is the substrate but is able to activate adenylate cyclase when 2-fluoro ATP is the substrate. The inability of certain analogs of adenosine, with bulky groups substituted for hydrogen at the 8 position of the adenine base, to activate adenylate cyclase and increase either lymphocyte or cardiac cell cAMP levels is consistent with the designation of the high anti conformation as being the conformation required for the activation of adenylate cyclase. An understanding of the glycosidic conformation required by the extracellular adenosine receptor of the adenosine molecule provides the basis for designing nucleoside analogs of adenosine that will exert a desired effect on cAMP levels. The avoidance of unwanted immunosuppressive or cardiotoxic effects can be arranged by structural changes that prohibit the high anti conformation.
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PMID:Conformational basis for the activation of adenylate cyclase by adenosine. 26 18

Adenosine receptor agonists increased cyclic AMP in cultures of bovine corneal endothelium up to 12-fold over control. Effects were dose-dependent between 1 microM and 0.5 mM adenosine. N6-methyladenosine produced a greater maximal effect but was approximately 10-fold less potent. Isoproterenol and N6-methyladenosine produced an additive response. Propranolol blocked the isoproterenol, but not the adenosine effect on cyclic AMP. Adenine-9-beta-D-arabinofuranoside had no effect on cyclic AMP alone, but inhibited stimulations by N6-methyladenosine, isoproterenol and forskolin. These data indicate the presence of specific adenosine receptors which stimulate adenylate cyclase in cultured bovine corneal endothelium.
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PMID:Adenosine regulation of cyclic AMP in corneal endothelium. 285 35