Endothelin, a peptide inhibitor of Na(+)-K(+)-ATPase in intact renaltubular epithelial cells

Journal Article · Fri Dec 01 04:00:00 EST 1989 · American Journal of Physiology; (USA)

OSTI ID:7195059

Zeidel, M L; Brady, H R; Kone, B C; Gullans, S R ^[1]

---

1. Brigham and Women's Hospital, Boston, MA (USA)

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.

• OSTI ID: 7195059
• Journal Information: American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 257; ISSN 0002-9513; ISSN AJPHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACID ANHYDRASES
ALKALI METAL COMPOUNDS
ALKALI METAL ISOTOPES
ALKALI METALS
ANIMAL TISSUES
ANIMALS
ATP-ASE
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
CARDIOVASCULAR AGENTS
DAYS LIVING RADIOISOTOPES
DRUGS
ELEMENTS
ENDOTHELIUM
ENZYME INHIBITORS
ENZYMES
HYDROLASES
IN VITRO
INHIBITION
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KIDNEYS
KINETICS
MAMMALS
MEMBRANE TRANSPORT
METALS
MINUTES LIVING RADIOISOTOPES
NONMETALS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
OXYGEN
PEPTIDES
PHOSPHOHYDROLASES
POTASSIUM COMPOUNDS
PROTEINS
RABBITS
RADIOISOTOPES
REACTION KINETICS
RUBIDIUM
RUBIDIUM 86
RUBIDIUM ISOTOPES
SODIUM COMPOUNDS
TISSUES
TRACER TECHNIQUES
TUBULES
UPTAKE
VASOCONSTRICTORS
VERTEBRATES