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Am J Physiol Cell Physiol 265: C934-C938, 1993;
0363-6143/93 $5.00
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AJP - Cell Physiology, Vol 265, Issue 4 C934-C938, Copyright © 1993 by American Physiological Society

ARTICLES

Adenosine A1 receptors and erythropoietin production

T. Ohigashi, J. Brookins and J. W. Fisher
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.

N6-cyclopentyladenosine (CPA), a selective adenosine A1 receptor agonist, in a concentration range of 10(-9) to 10(-7) M, produced a significant decrease in erythropoietin (EPO) levels in a human hepatocellular carcinoma (Hep G2) cell culture (medium levels of EPO, 91.81 +/- 1.61 and 94.36 +/- 0.97% of control, respectively) after 24 h incubation in a hypoxic atmosphere. CPA, at a concentration of 10(-9) M, also produced a significant decrease in Hep G2 cell levels of adenosine 3',5'-cyclic monophosphate (cAMP; 78.13 +/- 3.89% of control) after 2 h incubation. CPA (10(-9) M) also significantly inhibited forskolin-stimulated increases in EPO production and cAMP accumulation in Hep G2 cells. On the other hand, 2-[p-(2-carboxyethyl)phenethyl-amino]-5'-N-ethylcarboxamidoadenosine (CGS-21680), a selective adenosine A2-receptor agonist, produced no significant change in EPO production in a dose range of 10(-10) to 10(-6) M but increased cAMP accumulation at 10(-6) M. A1-receptor binding assays using N6-[3H]cyclohexyladenosine revealed a single type of adenosine receptor binding site on Hep G2 cell membranes with a dissociation constant of 71.4 nM and a binding capacity of 1,530 fmol/mg protein. These results indicate that Hep G2 cells contain high-affinity adenosine A1 receptors that are linked to decreased cAMP accumulation and EPO production.


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Lack of effect of extracellular adenosine generation and signaling on renal erythropoietin secretion during hypoxia
Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1501 - F1511.
[Abstract] [Full Text] [PDF]


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