Processing of adenosine receptor agonists in rat and human whole blood

A stability study of adenosine receptor agonists in rat and human whole blo od was performed. The compounds were incubated at 37 degrees in fresh blood , and aliquots of the incubation mixture were hemolyzed at regular time int ervals and analyzed with HPLC. N-6-cyclopentyladenosine (CPA) and N-6-cyclo butyladenosine (CBA) were degraded, whereas N-6 cyclohexyladenosine, N(6)cy cloheptyladenosine and N-6-sulfophenyladenosine were not. 2-Chloroadenosine had a half-life very similar to that of CPA. However, the 2'-, 3'-, and 5' -deoxyribose derivatives of CPA remained intact. The nucleoside transport i nhibitor nitrobenzylthioinosine attenuated CBA and CPA metabolism in rat bl ood as did the inhibitor of adenosine deaminase erythro-9-(2-hydroxy-3-nony l)adenine, albeit at relatively high concentrations. Complete blockade of C BA and CPA degradation was achieved by a preincubation of rat and human blo od with the adenosine kinase (AK) inhibitor 5'-amino-5'-deoxyadenosine. We conclude that the two adenosine analogues are metabolized by AK both in rat and in human whole blood. BIOCHEM PHARMACOL 56;12:1625-1632, 1998. (C) 199 8 Elsevier Science Inc.