Regulation of Macrophage Lysosomal Secretion by Adenosine, Adenosine Phosphate Esters, and Related Structural Analogues of Adenosine

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Abstract
Zymosan particle-stimulated β -galactosidase secretion by mouse peritoneal macrophages was found to be inhibited by micromolar concentrations of adenosine, AMP, ADP, and ATP. Inhibition by all four agents was increased to approximately 80% by adding erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA; 10 μM) an adenosine deaminase inhibitor, to the incubation medium. The inhibition of lysosomal enzyme secretion by ATP, ADP, and AMP was reversed by adding α,β -methylene ADP (100 μM), a 5′-nucleotidase inhibitor, to the incubation medium. Inhibition by adenosine, however, was unaffected byα,β -methylene ADP indicating that the inhibition by AMP, ADP, and ATP only occurred after they had been converted to adenosine by cell surface phosphohydrolases, including 5′-nucleotidase. Theophylline, a competitive antagonist of the binding of adenosine to plasma membrane adenosine receptors, failed to reverse the inhibitory effect of adenosine indicating the probable site of adenosine action to be intracellular. Other purine nucleosides, e.g., guanosine, and several purine and ribose- modified structural analogues of adenosine also inhibited zymosan-stimulated β -galactosidase secretion, while xanthosine and certain pyrimidine nucleosides, e.g., thymidine, were inactive in this respect.

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