Phorbol ester down-regulates glucagon stimulated taurocholate uptake in hepatocytes

Conference · Fri Mar 15 00:00:00 EST 1991 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:5173669

Simpser, E; Divald, A; Karl, P I; Fisher, S E ^[1]

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1. North Shore Univ. Hospital, Manhasset, NY (United States)

Glucagon (G) enhances bile flow and stimulates bile acid uptake by hepatocytes, although the mechanism of action is unclear. G may stimulate bile acid uptake by increasing intracellular cAMP concentration. Cyclic cAMP dependent cell functions may be modulated by protein kinase C. The authors evaluated the interaction of G-induced cAMP formation and PKC activation on bile acid uptake by rat hepatocytes. The effect of PKC activation by Phorbol-12,13-dibutyrate (PDBu) on intracellular cAMP or taurocholate (TC) uptake in unstimulated or G-stimulated isolated rat hepatocytes was investigated. {sup 3}H-TC uptake was measured 5, 10, 20 and 30 min after the addition of G. The effect of db-cAMP {plus minus} PDBu was also evaluated. Intracellular cAMP was measured by RIA. G stimulation increased TC uptake at all time points, with maximum stimulation from 10-20 min. PDBu virtually abolished the G effect. Uptake kinetics showed only a change in Vmax. PDBu had no effect on unstimulated TC uptake. PDBu did not alter the G-stimulated intracellular cAMP rise. PDBu decreased TC uptake even when hepatocytes were treated with db-cAMP. G-stimulation of hepatic TC uptake coincided with a rise in intracellular cAMP, although only low levels of cAMP were necessary to achieve maximum TC uptake. Calcium depletion caused 20% decrease in basal TC uptake, but did not alter the pattern of G-stimulation of TC uptake, but did not alter the pattern of G-stimulation of TC uptake nor the inhibitory effects of PDBu. PKC down-regulates G-stimulated TC uptake via mechanisms which appear to be independent of changes in either intracellular cAMP or calcium.

• OSTI ID: 5173669
• Report Number(s): CONF-9104107-; CODEN: FAJOE
• Journal Information: FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 5:5; Conference: 75. annual meeting of the Federation of American Societies for Experimental Biology (FASEB), Atlanta, GA (United States), 21-25 Apr 1991; ISSN 0892-6638
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BILE ACIDS
UPTAKE
GLUCAGON
BIOCHEMICAL REACTION KINETICS
PHORBOL ESTERS
BIOLOGICAL EFFECTS
AMP
LIVER CELLS
PHOSPHOTRANSFERASES
RADIOIMMUNOASSAY
TRITIUM COMPOUNDS
ANIMAL CELLS
BIOASSAY
CARBOXYLIC ACIDS
CARCINOGENS
DIAGNOSTIC TECHNIQUES
ENZYMES
ESTERS
HORMONES
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
IMMUNOASSAY
IMMUNOLOGY
ISOTOPE APPLICATIONS
KINETICS
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PEPTIDES
PHOSPHORUS-GROUP TRANSFERASES
POLYPEPTIDES
PROTEINS
RADIOASSAY
RADIOIMMUNODETECTION
RADIOIMMUNOLOGY
REACTION KINETICS
SOMATIC CELLS
STEROIDS
STEROLS
TRACER TECHNIQUES
TRANSFERASES
560300* - Chemicals Metabolism & Toxicology