AJP - Cell Physiology, Vol 249, Issue 1 3-C8, Copyright © 1985 by American Physiological Society
Role of prostaglandins in hypoxia-stimulated erythropoietin production
A. Kurtz, W. Jelkmann, J. Pfeilschifter and C. Bauer
The role of prostaglandins in the mediation of hypoxia-stimulated
erythropoietin (Ep) production by cultured rat renal mesangial cells was
examined. It was found that an increase in prostaglandin E2 (PGE2)
production accompanied the rise in Ep due to hypoxia (2% O2). The
hypoxia-stimulated increase in Ep production was abolished in the presence
of the cyclooxygenase inhibitor indomethacin (10(-5) M). When PGE2 (10(-6)
M was added simultaneously with indomethacin, however, no diminution in
hypoxia-stimulated Ep production was observed. Addition of arachidonic acid
(AA, 10(-5) M), PGE2 (10(-6) M), or PGI2 (10(-4) M) enhanced Ep production
under normoxic conditions (20% O2), while PGF2 alpha (10(-6) M) had no
effect on Ep production. AA, PGE2, and PGI2 were found to stimulate
adenosine 3',5'-cyclic monophosphate formation by the cultured mesangial
cells. Enhancement of adenylate cyclase activity by forskolin (10(-5) M)
also increased Ep production in the cell cultures. Our results suggest that
hypoxia-stimulated Ep production by cultured mesangial cells is mediated by
prostaglandins with subsequent stimulation of adenylate cyclase activity.
