AJP - Cell Physiology, Vol 259, Issue 3 C427-C431, Copyright © 1990 by American Physiological Society
Increased secretion of erythropoietin in human renal carcinoma cells in response to atrial natriuretic factor
M. Ueno, I. Rondon, B. Beckman, J. Brookins, J. Nakashima, F. E. Cole and J. W. Fisher
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
The present studies were undertaken to assess the effects of atrial
natriuretic factor (ANF) on erythropoietin (Ep) secretion in Ep-producing
renal carcinoma (RC) cells using a sensitive radioimmunoassay for Ep. Human
ANF produced a significant dose-related increase in Ep secretion at
concentrations of 10(-7) and 10(-6) M when compared with vehicle controls.
ANF (greater than or equal to 10(-9) M) also significantly increased the
intracellular guanosine 3',5'-cyclic monophosphate (cGMP) concentration
after 5-min incubation with the RC cells. Scatchard analysis of the human
125I-labeled ANF binding data indicated that the RC cells contain a single
class of binding sites with a dissociation constant (Kd) of 93 +/- 1 pM and
a binding capacity of 2,190 +/- 750 sites/cell. Incubation of the RC cells
with 8-bromo-cGMP in concentrations of 10(-7)-10(-5) M also produced a
significant dose-related enhancement of Ep secretion. These findings
suggest that the increase in Ep secretion in response to ANF can be
attributed, at least in part, to activation of guanylate cyclase, which is
coupled to specific ANF receptors on the RC cell.
