Adenosine A(2A) and A(2B) receptor activation of erythropoietin production.
We have examined the effects of adenosine receptors and protein kinases A and C in the regulation of erythropoietin (Epo) production using hepatocellular carcinoma (Hep3B) cells in culture and in vivo in normal mice under normoxic and hypoxic conditions. CGS-21680, a selective adenosine A(2A) agonist, significantly increased levels of Epo in normoxic Hep3B cell cultures and in serum of normal mice under both normoxic and hypoxic conditions. CGS-21680 also produced a significant increase in Epo mRNA levels in Hep3B cell cultures. SCH-58261, a selective adenosine A(2A) receptor antagonist, significantly inhibited the increase in medium levels of Epo in Hep3B cell cultures exposed to hypoxia (1% O(2)). Enprofylline, a selective adenosine A(2B) receptor antagonist, significantly inhibited the increase in plasma levels of Epo in normal mice exposed to hypoxia. Chelerythrine chloride, an antagonist of protein kinase C activation, significantly inhibited hypoxia-induced increases in serum levels of Epo in normal mice. A model is presented for adenosine in hypoxic regulation of Epo production that involves kinases A and C and phospholipase A(2) pathways.
Fisher
J W
JW
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112-2699, USA. jfisher@tulane.edu
Brookins
J
J
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000470:Alkaloids; D053119:Benzophenanthridines; D006528:Carcinoma, Hepatocellular; D004789:Enzyme Activation / Q000187:drug effects; D004921:Erythropoietin / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms; D010617:Phenanthridines / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D014230:Triazoles / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014970:Xanthines / Q000494:pharmacology
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D000470:Alkaloids; D053119:Benzophenanthridines; D010617:Phenanthridines; D010627:Phenethylamines; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1; D014230:Triazoles; D014970:Xanthines; D004921:Erythropoietin; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C034347:enprofylline; C016299:chelerythrine; D011493:Protein Kinase C; D000241:Adenosine