Adenosine A(2A) and A(2B) receptor activation of erythropoietin production.

Abstract

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.

• Authors: J W Fisher, J Brookins
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 281 Issue 5 Pg. F826-32 (Nov 2001) ISSN: 1931-857X [Print] United States
• PMID: 11592940 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
• Alkaloids
• Benzophenanthridines
• Phenanthridines
• Phenethylamines
• Purinergic P1 Receptor Antagonists
• Pyrimidines
• RNA, Messenger
• Receptor, Adenosine A2A
• Receptor, Adenosine A2B
• Receptors, Purinergic P1
• Triazoles
• Xanthines
• Erythropoietin
• 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
• enprofylline
• chelerythrine
• Protein Kinase C
• Adenosine

Topics

• Adenosine (analogs & derivatives, pharmacology)
• Alkaloids
• Benzophenanthridines
• Carcinoma, Hepatocellular
• Enzyme Activation (drug effects)
• Erythropoietin (biosynthesis, genetics)
• Humans
• Liver Neoplasms
• Phenanthridines (pharmacology)
• Phenethylamines (pharmacology)
• Protein Kinase C (antagonists & inhibitors, metabolism)
• Purinergic P1 Receptor Antagonists
• Pyrimidines (pharmacology)
• RNA, Messenger (analysis)
• Receptor, Adenosine A2A
• Receptor, Adenosine A2B
• Receptors, Purinergic P1 (physiology)
• Triazoles (pharmacology)
• Tumor Cells, Cultured
• Xanthines (pharmacology)