Effect of nitric oxide donors on extracellular ATP, ADP, and AMP catabolism in rat hippocampal synaptosomes

Extracellular adenine nucleotides acting as signaling molecules are inactiv ated by hydrolysis catalyzed by ectonucleotidases. Adenosine triphosphate ( ATP) diphosphohydrolase (apyrase, EC 3.6.1.5) and 5'-nucleotidase (EC 3.1.3 .5) are involved in an enzymatic chain for the hydrolysis of ATP to adenosi ne in the synaptic cleft. In this study, we investigated the in vitro effec t of nitric oxide (NO) donors on extracellular ATP, adenosine diphosphate ( ADP), and adenosine monophosphate (AMP) catabolism in hippocampal synaptoso mes of rats. We evaluated the effect of the incubation time on ATP, ADP, an d AMP hydrolysis in the absence and in the presence of 1 mM sodium nitropru sside (SNP). The inhibitory effect of SNP increased with the incubation tim e and the maximal inhibition was observed after 180 min for both enzyme act ivities. The inhibition observed attained a maximum at 1 mM SNP for ATP, AD P, and AMP hydrolysis, with the enzyme activities being markedly reduced at this concentration of SNP. However, other NO donors tested, such as S-nitr oso-N-acetyl-penicillamine and isosorbide dinitrate, did not affect the enz yme activities. The effect of the NO donor, SNP, on extracellular ATP and A DP catabolism was increased by the addition of the thiol glutathione but th is effect was not observed on extracellular AMP catabolism. The results sug gest that the increased production of NO could have a modulatory role on th e ectonucleotidase activities. (C) 2001 Elsevier Science Inc.