Studies of receptor-stimulated inositol lipid metabolism should focus upon measurements of inositol lipid breakdown

Michell, Robert H.; Kirk, C J

doi:10.1042/bj1980247

Cited by 31 publications

(13 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When these studies were initiated it appeared that the metabolism of polyphosphoinositides was subject to few very rapid perturbations by hormones or neurotransmitters (for review, see ). However, it has since become apparent that this was an incorrect view; several stimuli provoke very rapid breakdown and/or turnover of Ptdlns(4,5)P2, and maybe also PtdIns4P, in a variety of cells (Abdel-Latif et Kirk et al, 1981b;Michell et al, 1981;Soukup & Schanberg, 1982;Billah & Lapetina, 1982;Weiss et al, 1982;Kirk, 1982;Berridge, 1982;Putney, 1982;Berridge et al, 1983;Putney et al, 1983). The effective ligands are those that both mobilize Ca2+ in the cytosol of stimulated cells and cause the disappearance of some fraction of the cell's Ptdlns (previously assumed to indicate its breakdown).…”

Section: Discussionmentioning

confidence: 99%

“…An obvious and mechanistically economical possibility is that the activation of a single metabolic reaction leads to the decreases in the concentrations of all three inositol lipids. As realised first by , the two most likely candidates for this primary step are breakdown of Ptdlns catalysed by the PtdIns-specific phospholipase C of the cytosol (Michell, 1975;Irvine et al 1982;Shukla, 1982) or breakdown of polyphosphoinositides catalysed by a plasma-membrane phosphodiesterase similar to that of the erythrocyte (Abdel-Latif et al, 1977Hawthorne & Pickard, 1979;Kirk et al, 1981b;Michell et al, 1981;Downes & Michell, 1982a,b). Final confirmation that a phosphodiesterase is indeed implicated was recently obtained by Berridge etal.…”

Section: The Relationship Between Stimulation Of Polyphosphoinositidementioning

confidence: 99%

“…By contrast, our recent experiments, which are reported here, suggest that breakdown of Ptdlns(4,5)P2 (and perhaps also PtdIns4P) may precede the previously reported Ptdlns 'breakdown'. Some of these studies have been described briefly in the proceedings of recent meetings (Michell et al, 1981Kirk et al, 1981b;Creba et al, 1981;.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Rapid breakdown of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in rat hepatocytes stimulated by vasopressin and other Ca2+-mobilizing hormones

Creba¹,

Downes²,

Hawkins³

et al. 1983

Biochemical Journal

Self Cite

541

211

View full text Add to dashboard Cite

Rat hepatocytes rapidly incorporate [32P]Pi into phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]; their monoester phosphate groups approach isotopic equilibrium with the cellular precursor pools within 1 h. Upon stimulation of these prelabelled cells with Ca2+-mobilizing stimuli (V1-vasopressin, angiotensin, alpha 1-adrenergic, ATP) there is a rapid fall in the labelling of PtdIns4P and PtdIns(4,5)P2. Pharmacological studies suggest that each of the four stimuli acts at a different population of receptors. Insulin, glucagon and prolactin do not provoke disappearance of labelled PtdIns4P and PtdIns(4,5)P2. The labelling of PtdIns4P and PtdIns(4,5)P2 in cells stimulated with vasopressin or angiotensin initially declines at a rate of 0.5-1.0% per s, reaches a minimum after 1-2 min and then returns towards the initial value. The dose-response curves for the vasopressin- and angiotensin-stimulated responses lie close to the respective receptor occupation curves, rather than at the lower hormone concentrations needed to evoke activation of glycogen phosphorylase. Disappearance of labelled PtdIns4P and PtdIns(4,5)P2 is not observed when cells are incubated with the ionophore A23187. The hormone-stimulated polyphosphoinositide disappearance is reduced, but not abolished, in Ca2+-depleted cells. These hormonal effects are not modified by 8-bromo cyclic GMP, cycloheximide or delta-hexachlorocyclohexane. The absolute rate of polyphosphoinositide breakdown in stimulated cells is similar to the rate previously reported for the disappearance of phosphatidylinositol [Kirk, Michell & Hems (1981) Biochem. J. 194, 155-165]. It seems likely that these changes in polyphosphoinositide labelling are caused by hormonal activation of the breakdown of PtdIns(4,5)P2 (and may be also PtdIns4P) by the action of a polyphosphoinositide phosphodiesterase. We therefore suggest that the initial response to hormones is breakdown of PtdIns(4,5)P2 (and PtdIns4P?), and that the simultaneous disappearance of phosphatidylinositol might be a result of its consumption for the continuing synthesis of polyphosphoinositides.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: The Relationship Between Stimulation Of Polyphosphoinositidementioning

confidence: 99%

See 1 more Smart Citation

Rapid breakdown of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in rat hepatocytes stimulated by vasopressin and other Ca2+-mobilizing hormones

Creba¹,

Downes²,

Hawkins³

et al. 1983

Biochemical Journal

Self Cite

541

211

View full text Add to dashboard Cite

show abstract

“…Our current findings, how¬ ever, are inconsistent with this hypothesis, and force an adjustment of our model of the confluent pathways involved in phosphoinositide-associated signal trans¬ duction. There is now an appreciable consensus that the phosphodiesteratic hydrolysis of phosphoinositides is among the earliest of intracellular events to be promoted by receptor activation, with consequent resynthesis as an attendant, latent process (for reviews see Micheli & Kirk, 1981;Gershengorn, 1985;Hokin, 1985). Dopaminergic attenuation of phospholipid radiolabelling must, therefore, occur through some mechanism other than an inhibitor of phosphoinositide catabolism.…”

Section: Discussionmentioning

confidence: 99%

Dopamine does not attenuate phosphoinositide hydrolysis in rat anterior pituitary cells

Canonico¹,

Jarvis²,

Judd³

et al. 1986

Journal of Endocrinology

View full text Add to dashboard Cite

The hydrolysis of membrane phosphatidylinositol to yield [3H]labelled inositol phosphates by anterior pituitary cells was stimulated significantly by angiotensin II, TRH and neurotensin over a broad range of concentrations. These secretagogues also stimulated release of prolactin. Although the coincident incubation of dopamine with these agents resulted in a marked diminution of prolactin release, no concomitant reduction in inositol phosphate production was observed. In addition, bromocriptine, a potent agonist of dopamine, also proved ineffective in blunting stimulated phosphatidylinositol catabolism. Although it slightly inhibited basal rates of inositol tris-, bis- and monophosphate production, these results show that the secretagogue-mediated enhancement of phosphatidylinositol catabolism may be correlated with an increased release of prolactin and that the inhibition of hormone release produced by dopamine is not achieved by reducing basal or secretagogue-mediated inositol phosphate production.

show abstract

“…These compounds have been shown to be metabolically very active in brain and are thought to be intimately involved with synaptic processes as well as other membrane-receptor-mediated responses (see reviews bj7 Michell, 1975;Hawthorne and Pickard, 1979;13erridge, 1981). The actual role of phosphoinositicle metabolism in these processes remains unclear, and some aspects are controversial (Michell and Kirk, 1981;Hawthorne, 1982;Michell, 1982). Therle is little doubt, however, of the widespread, and perhaps universal, involvement of phosphoinositide metabolism in stimulus-response coupling.…”

Section: Discussionmentioning

confidence: 99%

The Influence of Specific Phospholipids on the Interaction of Hexokinase with the Outer Mitochondrial Membrane

Moller

Wilson

1983

Journal of Neurochemistry

View full text Add to dashboard Cite

Repeated washing of a brain mitochondrial fraction results in a progressive decrease in the proportion of mitochondrially bound hexokinase that can be solubilized during a subsequent incubation with glucose-6-phosphate (glucose-6-P). Phospholipids removed during the washing procedure can be added back to washed mitochondria, resulting in enhancement of the solubilization by glucose-6-P. Column and thin-layer chromatographic methods have been used to isolate and identify active phospholipids. Additional studies were performed with purified lipids obtained commercially. Both lysophospholipids and acidic phospholipids were active in enhancing solubilization of hexokinase by glucose-6-P. Phospho-inositides, particularly diphosphoinositide, were quite effective, raising the possibility that the actively metabolized phosphoinositides may be involved in regulation of hexokinase binding in vivo.

show abstract

Studies of receptor-stimulated inositol lipid metabolism should focus upon measurements of inositol lipid breakdown

Cited by 31 publications

References 10 publications

Rapid breakdown of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in rat hepatocytes stimulated by vasopressin and other Ca2+-mobilizing hormones

Rapid breakdown of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in rat hepatocytes stimulated by vasopressin and other Ca2+-mobilizing hormones

Dopamine does not attenuate phosphoinositide hydrolysis in rat anterior pituitary cells

The Influence of Specific Phospholipids on the Interaction of Hexokinase with the Outer Mitochondrial Membrane

Contact Info

Product

Resources

About