Hormone-sensitive hepatic Na/sup +/-pump: evidence for regulation by diacylglycerol and tumor promoters

Journal Article · Wed Nov 05 04:00:00 EST 1986 · J. Biol. Chem.; (United States)

OSTI ID:7093572

Lynch, C J; Wilson, P B; Blackmore, P F; Exton, J H

Ouabain-sensitive /sup 86/Rb/sup +/ uptake by isolated rat hepatocytes was studied to elucidate how Ca/sup 2 +/-mobilizing hormones stimulate the Na/sup +/-pump. Stimulation of this uptake was observed with concentrations of vasopressin ((8-arginine)vasopressin, AVP), angiotensin II, and norepinephrine which elicited Ca/sup 2 +/ mobilization and phosphorylase activation. These results suggested that changes in cytosolic Ca/sup 2 +/, mediated by inositol trisphosphate, might trigger sodium pump stimulation by AVP. However, in hepatocytes incubated in Ca/sup 2 +/-free Krebs-Henseleit buffer, Na/sup +/-pump activity was not altered over 15 min by either 1.5 mM EGTA or 1.5 mM Ca/sup 2 +/. Furthermore, incubation of cells in 5 mM EGTA for 15-30 min drastically impaired the ability of AVP to increase cytosolic Ca/sup 2 +/, but only modestly attenuated AVP-stimulated Na/sup +/-pump activity. Two tumor promoters, phorbol myristate acetate (PMA) and mezerein, stimulated Na/sup +//K/sup +/-ATPase-mediated transport activity. Similarly, addition of synthetic diacylglycerols or of exogenous phospholipase C from Clostridium perfringens to increase endogenous diacylglycerol levels also resulted in a stimulation of the Na/sup +/-pump in the absence of changes in cytosolic or total cellular Ca/sup 2 +/ levels. Stimulation of the Na/sup +/-pump by the combination of maximal concentrations of PMA and AVP did not produce an additive response, and both agents displayed a transient time course, suggesting that the two agents share a common mechanism. Stimulation of the Na/sup +/-pump by AVP and PMA was not blocked by amiloride analogs which inhibit Na/sup +//H/sup +/ exchange, but these compounds blocked the action of insulin. These data suggest that the elevated Na/sup +//K/sup +/-ATPase-mediated transport activity observed in hepatocytes following exposure to Ca/sup 2 +/-mobilizing hormones is a consequence of stimulated diacylglycerol formation and may involve protein kinase C.

• Research Organization: Vanderbilt Univ., Nashville, TN
• OSTI ID: 7093572
• Journal Information: J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 261:31; ISSN JBCHA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ACID ANHYDRASES
ALCOHOLS
ALKALI METAL COMPOUNDS
ALKALI METAL ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
ATP-ASE
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMISTRY
CALCIUM COMPOUNDS
CARCINOGENS
CATIONS
CHARGED PARTICLES
CHEMISTRY
DAYS LIVING RADIOISOTOPES
ENZYMES
ESTERS
GLYCEROL
HYDROLASES
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
IONS
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LIVER CELLS
MAMMALS
MEMBRANE TRANSPORT
MINUTES LIVING RADIOISOTOPES
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHORBOL ESTERS
PHOSPHOHYDROLASES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PROMOTERS
RADIOISOTOPES
RATS
RODENTS
RUBIDIUM 86
RUBIDIUM ISOTOPES
SODIUM COMPOUNDS
SOMATIC CELLS
TRANSFERASES
TUMOR PROMOTERS
UPTAKE
VERTEBRATES