Role of Inositol Cyclic Phosphate in Stimulated Tissues

Freinkel, Norbert; Dawson, R. M. C.

doi:10.1038/243535a0

Cited by 30 publications

(9 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Possible functions for enhanced turnover of the phosphorylinositol group of phosphatidylinositol include intracellular production of myo-inositol 1,2-cyclic phosphate (Michell & Lapetina, 1972) and changes in the lipid patterns of cell membranes (see Hawthorne, 1973;Lapetina & Michell, 1973a, for reviews). The suggestion that the production ofthe cyclic ester might be of physiological significance has been criticized by Freinkel & Dawson (1973) who failed to find either a function for or the intracellular existence of either this compound or myo-inositol 1-phosphate. However, both the data presented here and those of Hokin (1973) indicate that some form of inositol phosphate must be produced in stimulated cells, even if only transiently.…”

Section: Change (Y)mentioning

confidence: 99%

“…Two types of possible mechanisms for this effect, namely changes in the specific radioactivity of intracellular precursor pools and direct enhancement of the biosynthesis of phosphatidylinositol de novo, appear to have been excluded by existing experimental data. A third type of mechanism in which the primary event evoked by the stimulus is the removal of the phosphorylinositol group from phosphatidylinositol has been favoured by several authors (Hokin, 1967;De Robertis, 1971;Michell & Lapetina, 1972;Lapetina & Michell, 1973a;Freinkel & Dawson, 1973;Lapetina & Michell, 1974). Further alternatives include stimulation of either diacylglycerol kinase (Hokin & Hokin, 1959;Hollander et al, 1970) or phosphatidate phosphohydrolase (Schacht & Agranoff, 1973;Yagihara et al, 1973).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Breakdown of phosphatidylinositol provoked by muscarinic cholinergic stimulation of rat parotid-gland fragments

Jones

Michell

1974

Biochemical Journal

107

View full text Add to dashboard Cite

When rat parotid fragments that had been labelled with (32)P in vivo were exposed to high concentrations of acetylcholine, radioactivity was lost from phosphatidylinositol but not from other phospholipids. Simultaneously the concentration of phosphatidylinositol in the tissue decreased. If previously unlabelled tissue was incubated with (32)P(i) an increase in incorporation of radioactivity into phosphatidylinositol was observed during this decrease in concentration. The effects of acetylcholine were blocked by atropine, but not by tubocurarine. The response to acetylcholine was rapid, with up to one-third of the tissue's phosphatidylinositol disappearing within 5min. Similar effects were evoked by stimulation with methacholine and by high concentrations of tetramethylammonium ion; these responses were also atropine-sensitive and tubocurarine-insensitive. It is concluded that the event in inositol lipid metabolism that is affected by acetylcholine stimulation is removal of the phosphorylinositol group from the molecule; this is mediated through muscarinic cholinergic receptors. This is followed by a compensatory increase in the rate of synthesis of phosphatidylinositol, which has been described in detail in the past. These observations are compared with those of previous workers and are discussed in relation to the existing hypotheses relating to the significance of stimulus-provoked phosphatidylinositol turnover.

show abstract

Section: Change (Y)mentioning

confidence: 99%

mentioning

confidence: 99%

Breakdown of phosphatidylinositol provoked by muscarinic cholinergic stimulation of rat parotid-gland fragments

Jones

Michell

1974

Biochemical Journal

107

View full text Add to dashboard Cite

show abstract

“…However, investigations to date have L. Best and W.J. Malaisse: Phospholipids and islet function failed to provide conclusive evidence in favour of this hypothesis [52].…”

Section: Interrelationships Between Stimulated Phosphatidylinositol Mmentioning

confidence: 99%

Phospholipids and islet function

Best¹,

Malaisse²

1983

Diabetologia

View full text Add to dashboard Cite

There is an increasing number of examples of cells which, upon activation, display enhanced turnover of phospholipids, particularly the inositol-containing lipids and phosphatidic acid. Such an effect, commonly referred to as the phosphatidylinositol or PI effect, was first demonstrated in pancreactic exocrine tissue by Hokin and Hokin [1]. Subsequently, the list of examples of this effect has been extended to include a wide spectrum of agonist-receptor interactions and an even more diverse range of biological responses, including propagation of nerve impulses, cell motility, cell division and differentiation, and exocytosis. This topic has been extensively surveyed in recent years, notably by Michell and co-workers [2-4], Hawthorne et al. [5,6], Berridge [7] and Putney [8]. The aim of this review is to examine the evidence for enhanced phospholipid metabolism in pancreatic islets during stimulation and to speculate upon the possible role(s) that phospholipids may play in stimulus-secretion coupling. Figure I shows a simplified scheme for phospholipid interconversions in mammalian tissues, diacylglycerol forming an important intermediate both in the metabolism of phosphatidylcholine and phosphatidylethanolamine, and in the phosphatidylinositol cycle. Enhanced phospholipid metabolism during stimulation is generally confined to phosphatidic acid and the inositol-containing lipids. The key step in triggering turnover of the phosphatidylinositol cycle may be the breakdown of this lipid to diacylglycerol [2, 3, 6, 8] or as suggested by recent studies [7, 9, 10], the breakdown of one or both of the polyphosphoinositides (phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate) via specific phospholipases C. Nature of the Phosphatidylinositol EffectStudies of enhanced phospholipid turnover in cells are often based on the use of radioactive precursors (e. g. 32po43-, 3H-glycerol, 3H-inositol, labelled fatty acids). The rate of incorporation of precursor into lipid can be measured in the presence or absence of stimulus, providing an index of phospholipid synthesis (or resynthesis following breakdown). Alternatively, to assess phospholipid breakdown, the phospholipids may be prelabelled close to isotopic equilibrium, the unincorporated label removed and the tissue subsequently stimulated. These techniques should be combined ideally with measurements of phospholipid concentrations by chemical analysis. However, the limited amounts of tissue available using islets of Langerhans present considerable technical difficulties in measuring individual phospholipids, particularly those (such as the phosphoinositides) which constitute only a small proportion of the total cellular lipid. Enhanced Phospholipid Metabolism in Pancreatic IsletsIn a study of 32p-labelling of phospholipids in obese mouse islets, Fex and Lernmark [11] first showed that glucose caused increased labelling, most markedly in a fraction containing phosphatidylinositol and phosphatidylserine. Freinkel et al. [12,13] also noted that glucose stim...

show abstract

“…phagocytosis and pinocytosis; Karnovsky & Wallach, 1961), metabolites and ions (Resch & Ferber, 1972). Alternatively, Michell & Lapetina (1972) have suggested that enhanced phosphatidylinositol turnover reflects the increased production of myo-inositol 1:2-cyclic phosphate, to which they ascribed the role of a 'second messenger'; evidence in support of this suggestion is, however, presently lacking (Freinkel & Dawson, 1973). In spite of the above attractive arguments the significance of increased phosphatidylinositol metabolism and its relationship to cell activation remain uncertain.…”

mentioning

confidence: 99%

Relationship between enhanced turnover of phosphatidylinositol and lymphocyte activation by mitogens

Maino¹,

Hayman²,

Crumpton³

1975

Biochemical Journal

142

View full text Add to dashboard Cite

1. Various lectins [phaseolus vulgaris phytohaemagglutinin, Glycine max (soy-bean) agglutinin, Triticum vulgaris (wheat-germ) agglutinin and Axinella polyploides agglutinin] and antibodies to pig Ig (immunoglobulin) that are found by pig lymphocytes were assessed in terms of their capacities to stimulate lymphocyte transformation and to enhance phosphatidylinositol turnover. Transformation was measured after 45h of culture by incorporation of [6-(3)H]thymidine into DNA, whereas phosphatidylinositol metabolism was assessed after 1h of cultuis and G. max agglutinins and rabbit antibodies to pig Ig) increased phosphatidylinositol turnover, but non-transforming agents (T. vulgaris and A. polyploides agglutinins and Fab fragments of rabbit antibodies to pig Ig) failed to induce any significant enhancement. Subsequent cross-linkage of the bound, non-transforming Fab fragments with a goat antiserum to rabbit Ig stimulated transformation and phosphatidylinositol turnover. 3. Each transforming agent gave characteristic optimal dose responses that were similar for both phosphatidylinositol turnover and transformation. 4. The results indicate that activation of T- and B-lymphocytes is accompanied by enhanced phosphatidylinositol turnover and that in the case of B-cells this enhancement depends on the cross-linkage of surface receptors. They are consistent with the proposal that turnover represents an essential early step in the transformation process.

show abstract

Role of Inositol Cyclic Phosphate in Stimulated Tissues

Cited by 30 publications

References 13 publications

Breakdown of phosphatidylinositol provoked by muscarinic cholinergic stimulation of rat parotid-gland fragments

Breakdown of phosphatidylinositol provoked by muscarinic cholinergic stimulation of rat parotid-gland fragments

Phospholipids and islet function

Relationship between enhanced turnover of phosphatidylinositol and lymphocyte activation by mitogens

Contact Info

Product

Resources

About