AJP - Cell Physiology, Vol 257, Issue 6 C1101-C1107, Copyright © 1989 by American Physiological Society
Endothelin, a peptide inhibitor of Na(+)-K(+)-ATPase in intact renaltubular epithelial cells
M. L. Zeidel, H. R. Brady, B. C. Kone, S. R. Gullans and B. M. Brenner
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Endothelin, a potent vasoconstrictor released by vascular endothelial
cells, can induce natriuresis in vivo. These studies examined the
regulation of Na+ transport by endothelin in suspensions of rabbit proximal
tubule (PT) and inner medullary collecting duct (IMCD) cells. Endothelin
reduced oxygen consumption (QO2) by 18 +/- 1% in IMCD cells but did not
alter QO2 in PT cells. In IMCD cells, endothelin inhibited QO2 half
maximally at approximately 5 x 10(-12) M. Several lines of evidence
indicate that endothelin reduces QO2 by inhibiting the Na(+)-K(+)-ATPase.
1) Endothelin gave no further inhibition of QO2 after ouabain and blunted
the stimulatory effect of amphotericin B on QO2 (+29 +/- 4% in absence of
endothelin, 0 +/- 5% in presence of endothelin; n = 6 preparations, P less
than 0.001). 2) Endothelin inhibited ouabain-sensitive 86Rb+ uptake by 46.6
+/- 8.6% at 10 s and by 35.4 +/- 5.3% at 30 s without altering uptake at 60
min. 3) Addition of endothelin to IMCD cells induced a net K+ efflux with
an initial rate of 32.2 +/- 4.8 nmol.min-1.mg protein-1, consistent with
inhibition of the Na(+)-K(+)-ATPase. In contrast to the response observed
in intact cells, in permeabilized IMCD cells endothelin did not inhibit
ouabain-sensitive ATPase. Several observations indicated that prostaglandin
E2 (PGE2) mediates endothelin inhibition of Na(+)-K(+)-ATPase activity. 1)
The response to endothelin was blocked by ibuprofen in assays of QO2, net
K+ flux, and 86Rb+ uptake. 2) Endothelin and PGE2 gave equivalent,
nonadditive inhibition of ouabain-sensitive 86Rb+ uptake.(ABSTRACT
TRUNCATED AT 250 WORDS)
