A transient increase in diacylglycerols is associated with the action of vasopressin on hepatocytes

Hughes, B P; Rye, K.-A.; Pickford, Lesley B.; Barritt, Greg J.; Chalmers, A H

doi:10.1042/bj2220535

Cited by 52 publications

(29 citation statements)

References 45 publications

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“…A. Spitzer, unpublished work). (2) The accumulation of total DAG was sustained up to the last time analysed (10 min), a finding similar to that previously obtained for control cells [29][30][31][32] and at variance with the transient increase reported by others [33,34]. (3) The release of C18 0-and C20:4-DAG was detected before other DAG acyl groups.…”

Section: Discussionsupporting

confidence: 72%

Kinetics of diacylglycerol accumulation in response to vasopressin stimulation in hepatocytes of continuously endotoxaemic rats

Turco

Spitzer

1988

Biochemical Journal

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The content and composition of 1,2-diacyl-sn-glycerol (1,2-DAG) was determined in hepatocytes from saline (0.9 % NaCl)-and Escherichia coli endotoxin (ET)-infused rats upon continuous vasopressin (VP) (10-8 M) stimulation. In both experimental groups the accumulation of 1,2-DAG was detected after a lag period (2-5 min), was sustained up to the last time analysed (10 min), and C18 0-and C20 4-fatty-acid-containing-DAG accumulation preceded that of DAG containing other acyl groups. In hepatocytes from ET-infused rats the VP-induced accumulation of DAG was delayed and was decreased by 50 %, showing a C18:0/C20:4 molar ratio of 1.6 as compared with 1.1 for cells from saline-infused rats. A similar lower cellular response to VP stimulation was observed in cells prelabelled with [14C]C20 :4 fatty acid. The accumulation of [14C]C20 :4-DAG (lower in ET than in saline-infused rats) was paralleled by a decrease in phosphatidylinositol (PI) labelling, whereas phosphatidic acid showed a transient increase by 5 min in saline-but not in ET-infused rats. The present results demonstrate that the previously reported impairment in the early degradation of poly-PI and later in the 'PI cycle' during VP stimulation [Rodriguez de Turco & Spitzer (1987) Metab. Clin. Exp. 36,[753][754][755][756][757][758][759][760] is also reflected at the level of their phosphodiesteratic product, DAG. Moreover, the kinetics of the accumulation of DAG acyl groups is consistent with the idea that the initial release of C18:0-and C20:4-DAG (possibly derived from inositol lipids) could regulate the subsequent enlargement of this pool by stimulating a phospholipase C-mediated degradation of other phospholipids (e.g. phosphatidylcholine). INTRODUCTIONDuring endotoxicosis and sepsis, that is, in the face of detectable circulating levels of bacterial cell-wall components known as endotoxins, or live microbial organisms and their secretory products, hepatocytes sustained severe perturbations in the transmission of information from extracellular Cal2-mobilizing glycogenolytic hormones [1]. We have further characterized the interference by endotoxaemia in the regulation of cell metabolism linked to the inositol phospholipid/Ca2l signalling mechanism using rats continuously infused with a non-lethal dose of Escherichia coli endotoxin (ET) [2]. This model has been extensively used in our laboratory [3][4][5], owing to the fact that it reproduces many of the haemodynamic and metabolic perturbations observed during human 'Gram-negative' septicaemia [6,7]. Previous studies conducted 30 h after continuous ET-infusion (the morbid phase of the process) indicated a perturbation in Ca2l homoeostasis and phosphorylase activation when hepatocytes were challenged with vasopressin (VP) or adrenaline (epinephrine) [8,9] [12] observed that the ability of myo-inositol 1,4,5-trisphosphate (IP3) to release Ca2l from endoplasmic-reticulum stores in permeabilized hepatocytes from ET-infused rats was greatly diminished.It is well known that the early event triggered by Ca2+-mobi...

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Section: Discussionsupporting

confidence: 72%

Kinetics of diacylglycerol accumulation in response to vasopressin stimulation in hepatocytes of continuously endotoxaemic rats

Turco

Spitzer

1988

Biochemical Journal

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“…In vasopressin stimulated hepatocytes one laboratory reported enrichement in both stearic and arachidonic acid after 1 min of exposure to the agonist (21), while another found increases in stearic and less changes in arachidonic acid content (22). However the smaller increase ofarachidonic acid could have been due to oxidation ofthis labile fatty acid during the HPLC purification.…”

Section: Discussionmentioning

confidence: 99%

Glucose and carbachol generate 1,2-diacylglycerols by different mechanisms in pancreatic islets.

Peter-Riesch¹,

Fathi²,

Schlegel³

et al. 1988

J. Clin. Invest.

179

128

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Diacylglycerols (DAG) modulate secretory responses by the activation of protein kinase C. Early changes in DAG formation induced by the muscarinic receptor agonist carbachol were compared to those caused by the nutrient secretagogue glucose in pancreatic islets. Turnover rates of DAG were investigated in radiolabeling experiments, whereas changes in total mass and fatty acid composition of DAG were assessed by gas-liquid chromatography. When islet lipids were labeled to steady state in tissue culture with VHjglycerol, carbachol induced a rapid (10 s) and sustained increase of rHIDAG generation. In contrast, glucose stimulation failed to increase VHjglycerol containing DAG, and this was probably due to the isotopic dilution of the label secondary to enhanced glycolysis. This was substantiated by following the transfer of "4C from glucose into DAG. Within 1 min of acute exposure of islets to D[U-4CjC glucose at stimulatory concentrations, DAG labeling increased fivefold representing up to 2% of total glucose usage. Similar stimulation of 14C incorporation into other neutral lipids and inositol phospholipids was observed, suggesting the enhanced de novo synthesis of phosphatidic acid, the common precursor for DAG, and inositol phospholipids from glycolytic intermediates. Transfer of "C from glucose was not stimulated by agents such as carbachol and exogenous phospholipase C that act primarily on inositol phospholipid breakdown. The total mass of islet DAG was increased by 60% after both carbachol and glucose stimulation. However, analysis of the fatty acid composition of carbachol-generated DAG revealed at the early time point (10 s) a prevalent stearoyl-arachidonoyl configuration similar to that reported for inositol phospholipids. This pattern shifted to a DAG enriched in palmitic acid at a later time point. Glucose-stimulated islets displayed a predominance of palmitic acid containing DAG, indicating increased de novo synthesis of the, putative second messenger rather than its formation by inositol phospholipid hydrolysis. Indeed, steadystate labeling of these phospholipids with I3Hiinositol confirmed this idea since only carbachol caused detectable inositol phospholipid hydrolysis. Thus, although protein kinase C may be activated by both carbachol and glucose, the two secretagogues generate diacylglycerols through different mechanisms.

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“…A rapid and usually transient accumulation of DG associated with stimulated phosphoinositide breakdown has been demonstrated in platelets [21,63,116,146,148,204,236,254], pancreas [18,67], mast cells [144], 3T3 cells [108], pituitary cells [74,198,249], GH3 cells [75], and liver [142,302]. A rapid and usually transient accumulation of DG associated with stimulated phosphoinositide breakdown has been demonstrated in platelets [21,63,116,146,148,204,236,254], pancreas [18,67], mast cells [144], 3T3 cells [108], pituitary cells [74,198,249], GH3 cells [75], and liver [142,302].…”

Section: Diacylglyeerolmentioning

confidence: 99%

“…A rapid and usually transient accumulation of DG associated with stimulated phosphoinositide breakdown has been demonstrated in platelets [21,63,116,146,148,204,236,254], pancreas [18,67], mast cells [144], 3T3 cells [108], pituitary cells [74,198,249], GH3 cells [75], and liver [142,302]. Some studies [18,142] have suggested that only a part of this newly generated DG is due to phosphoinositide breakdown, and the rest is considered to arise from other lipids. Some studies [18,142] have suggested that only a part of this newly generated DG is due to phosphoinositide breakdown, and the rest is considered to arise from other lipids.…”

Section: Diacylglyeerolmentioning

confidence: 99%

The role of phosphoinositiees in signal transduction

1986

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A transient increase in diacylglycerols is associated with the action of vasopressin on hepatocytes

Cited by 52 publications

References 45 publications

Kinetics of diacylglycerol accumulation in response to vasopressin stimulation in hepatocytes of continuously endotoxaemic rats

Kinetics of diacylglycerol accumulation in response to vasopressin stimulation in hepatocytes of continuously endotoxaemic rats

Glucose and carbachol generate 1,2-diacylglycerols by different mechanisms in pancreatic islets.

The role of phosphoinositiees in signal transduction

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