Clinical Pharmacology of Preconditioning and Adenosinergic Drugs
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Adenosine’s formation is the simple consequence of a disequilibrium between dephosphorylation of ATP (’energy demand) and rephosphorylation (mitochondrial oxidative metabolism > energy supply). AMP, adenosine’s immediate precursor, is a most sensitive sensor of energy shortage.
Adenosine’s formation is small and temporarily. It is limited to the ischemic area within most vital organs and only when oxygen supply is insufficient to cope with the demand. Nature has even taken precautions to prevent spreading of this potent messenger to normoxic regions or organs by providing rapid catabolism in the endothelial cells lining the microvessels, and in erythrocytes.
Adenosine’s production initiates a cascade of effects. Its most prominent activity, microvascular vasodilatation, will be a first-aid measure to restore the balance. If not sufficient, more adenosine will accumulate and more receptors within reach may be triggered: demand will be moderated and there will be a delay in the start of a vicious circle of events leading to major organ damage.
KeywordsAdenosine Deaminase Nucleoside Transport Left Ventricular Ejection Time Mitochondrial Oxidative Metabolism European Stroke Prevention Study
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