Regulation of macrophage lysosomal secretion by adenosine, adenosine phosphate esters, and related structural analogues of adenosine.
Zymosan particle-stimulated beta-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 microM) an adenosine deaminase inhibitor, to the incubation medium. The inhibition of lysosomal enzyme secretion by ATP, ADP, and AMP was reversed by adding alpha, beta -methylene ADP (100 microM), a 5'-nucleotidase inhibitor, to the incubation medium. Inhibition by adenosine, however, was unaffected by alpha, beta -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 ribosemodified structural analogues of adenosine also inhibited zymosan-stimulated beta-galactosidase secretion, while xanthosine and certain pyrimidine nucleosides, e.g., thymidine, were inactive in this respect.
Riches
D W
DW
Watkins
J L
JL
Henson
P M
PM
Stanworth
D R
DR
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000227:Adenine Nucleotides / Q000494:pharmacology*; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004950:Esterases / Q000378:metabolism; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008247:Lysosomes / Q000201:enzymology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D011956:Receptors, Cell Surface / Q000187:drug effects; D011983:Receptors, Purinergic; D012636:Secretory Rate / Q000187:drug effects; D013329:Structure-Activity Relationship; D013806:Theophylline / Q000494:pharmacology; D014372:Tubercidin / Q000494:pharmacology
D000227:Adenine Nucleotides; D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; C018258:3-deazaadenosine; D006710:Homocysteine; C010192:9-(2-hydroxy-3-nonyl)adenine; D013806:Theophylline; C007957:homocysteine thiolactone; D004950:Esterases; D000225:Adenine; D000241:Adenosine; D014372:Tubercidin