Phorbol ester down-regulates glucagon stimulated taurocholate uptake in hepatocytes

Conference · Thu Mar 14 23:00:00 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--
• Journal Information: FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Vol. 5:5; ISSN FAJOE; ISSN 0892-6638
• Country of Publication: United States
• Language: English

Related Subjects

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