Effect of phorbol esters on mitochondrial actions of glucagon
Glucagon generates different second messenger signals in liver. It increases cAMP levels and elevates cytosolic Ca/sup 2 +/ levels by degradation of polyphosphoinositides. The phorbol ester 12-0-tetradecanoyl phorbol 13-acetate (TPA) inhibits glucagon-induced calcium mobilization, but not cAMP formation. TPA can thus be used to assess the role of Ca/sup 2 +/ and cAMP in the activation of mitochondrial processes. In isolated hepatocytes, glucagon increased the steady state NAD(P)H level, probably by activating mitochondrial Ca/sup 2 +/ dependent dehydrogenases. TPA inhibited the glucagon-induced NAD(P) reduction without affecting phosphorylase activation. The effects of glucagon and TPA on mitochondrial respiratory activity and calcium retention were tested after isolation of the mitochondria from perfused livers. Electron transport rates were increased by 15-25% and calcium retention time was increased four-fold after glucagon treatment. When livers were pretreated with TPA, glucagon had no effect on electron transport activity, but calcium retention was increased by the same factor. The results suggest that glucagon-induced calcium mobilization is required for the stimulation of the respiratory activity but not for the increased capacity to retain a calcium overload in the mitochondria.
- Research Organization:
- Thomas Jefferson Univ. Medical School, Philadelphia, PA
- OSTI ID:
- 6065805
- Report Number(s):
- CONF-870644-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 46:6; Conference: 78. annual meeting of the American Society of Biological Chemists conference, Philadelphia, PA, USA, 7 Jun 1987
- Country of Publication:
- United States
- Language:
- English
Similar Records
Calcium mobilization in permeabilized fibroblasts: effects of inositol trisphosphate, orthovanadate, mitogens phorbol ester, and guanosine triphosphate
Phorbol ester down-regulates glucagon stimulated taurocholate uptake in hepatocytes
Related Subjects
CALCIUM COMPOUNDS
MEMBRANE TRANSPORT
GLUCAGON
BIOLOGICAL FUNCTIONS
PHORBOL ESTERS
BIOLOGICAL EFFECTS
PHOSPHOLIPIDS
METABOLISM
AMP
ELECTRON TRANSFER
INHIBITION
LIVER
MITOCHONDRIA
NADP
OXIDOREDUCTASES
ALKALINE EARTH METAL COMPOUNDS
BODY
CARCINOGENS
CELL CONSTITUENTS
COENZYMES
DIGESTIVE SYSTEM
ENZYMES
ESTERS
FUNCTIONS
GLANDS
HORMONES
LIPIDS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANOIDS
ORGANS
PEPTIDE HORMONES
PEPTIDES
POLYPEPTIDES
PROTEINS
560300* - Chemicals Metabolism & Toxicology