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Title: Effect of phorbol esters on mitochondrial actions of glucagon

Abstract

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.

Authors:
; ;
Publication Date:
Research Org.:
Thomas Jefferson Univ. Medical School, Philadelphia, PA
OSTI Identifier:
6065805
Report Number(s):
CONF-870644-
Journal ID: CODEN: FEPRA
Resource Type:
Conference
Resource Relation:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States); Journal Volume: 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
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 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

Citation Formats

Cardellach, F., Moehren, G., and Hoek, J.B.. Effect of phorbol esters on mitochondrial actions of glucagon. United States: N. p., 1987. Web.
Cardellach, F., Moehren, G., & Hoek, J.B.. Effect of phorbol esters on mitochondrial actions of glucagon. United States.
Cardellach, F., Moehren, G., and Hoek, J.B.. 1987. "Effect of phorbol esters on mitochondrial actions of glucagon". United States. doi:.
@article{osti_6065805,
title = {Effect of phorbol esters on mitochondrial actions of glucagon},
author = {Cardellach, F. and Moehren, G. and Hoek, J.B.},
abstractNote = {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.},
doi = {},
journal = {Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)},
number = ,
volume = 46:6,
place = {United States},
year = 1987,
month = 5
}

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  • The effect of protein kinase C (PKC) inhibitors 1-(5-isoquinoline-sulfonyl)-2-methylpiperazine (H-7), polymyxin B (PMB), D-sphingosine (SPH), sangivamycin (SNG) and staurosporin (ST) on the action of PKC activators phorbol 12,13-dibutyrate (PDBu) and 12-o-tetradecanoylphorbol-13-acetate (TPA), on adrenergic neuroeffector events was investigated to determine the contribution of PKC in adrenergic transmission in the rat kidney. Infusion of TPA (5 x 10(-6) mM) or PDBu (6 x 10(-6) mM) produced renal vasoconstriction and enhanced the overflow of tritium elicited by periarterial renal nerve stimulation (RNS) (2 Hz) in the isolated rat kidney perfused with Tyrode's solution and prelabeled with (3H)norepinephrine. H-7 (2.7 x 10(-3) mM)more » and ST (2 x 10(-5) mM) did not alter RNS-induced overflow of tritium but attenuated the vasoconstrictor response to RNS and exogenous NE. PMB (1 x 10(-8) mM) and SPH (3.3 x 10(-4) mM) but not SNG (3.3 x 10(-3) mM) attenuated the RNS-induced overflow of tritium but increased the basal renal vascular tone and enhanced the vasoconstrictor response to RNS and exogenous NE. H-7, PMB, SPH, SNG or ST failed to alter the effects of PDBu to increase basal vascular tone and the overflow of tritium and the increase in renal vasoconstriction to RNS. PMB at 1 x 10(-9) mM but not at 1 x 10(-8) mM and SPH (3.3 x 10(-4) mM) but not H-7, SNG or ST inhibited the effect of TPA to increase the overflow of tritium. The effect of TPA on the vasoconstrictor response to RNS or to increase basal vascular tone was not altered by PKC inhibitors. These data suggest that in the rat kidney, PKC is either resistant to the actions of H-7, PMB, SPH, SNG and ST, or PDBu and TPA produce renal vasoconstriction and facilitate adrenergic transmission by a mechanism unrelated to PKC activation.« less
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  • Mannoheptulose (MH) affects pancreatic Islet cells to cause a drop in serum insulin and a rise in glucagon. This effect peaks 1 hr after injection and results in a 3-fold increase in serum glucose. Here they examined whether metabolic functions of liver mitochondria (mito) are altered by this change in hormone status. Rats fed ad lib on 12 hr light/dark cycles were given MH (2g/kg) or vehicle i.p. during the first 2 hrs of the light cycle. Liver mito were isolated 1 hr later. Acid-extracts were assayed for ATP+ADP+AMP (nmol/mg prot). Citrulline synthesis and pyruvate carboxylation rates (nmol/min/mg prot) weremore » assayed by following H(/sup 14/C)O/sub 3//sup -/ fixation in appropriate media. State 3 and 2,4-DNP-uncoupled respiratory rates (1/2 nmol O/sub 2//min/mg prot) were assayed polarographically with succinate. The effects of MH on mito are comparable to reported effects of glucagon injection. MH evokes acute reciprocal changes in insulin and glucagon that are highly reproducible. Thus, MH offers an interesting model for studying the effect of endogenous hormones on mito functions.« less
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