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PMID: 6309153 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Biochemical journal ·Vol. 212 ·No. 3 ·1983-06-15 ·Pages 733-47

Creba JA, Downes CP, Hawkins PT, Brewster G, Michell RH, Kirk CJ

Abstract

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.

MeSH Terms
Angiotensin II/pharmacology Animals Arginine Vasopressin/pharmacology Calcium/metabolism Dose-Response Relationship, Drug Hormones/pharmacology In Vitro Techniques Liver/cytology,drug effects,metabolism Phosphatidylinositol Phosphates Phosphatidylinositols/metabolism Phosphoric Monoester Hydrolases/metabolism Rats Rats, Inbred Strains Receptors, Cell Surface/drug effects Stimulation, Chemical
Chemicals
Hormones Phosphatidylinositol Phosphates Phosphatidylinositols Receptors, Cell Surface phosphatidylinositol 4-phosphate Angiotensin II Arginine Vasopressin Phosphoric Monoester Hydrolases phosphoinositide 5-phosphatase Calcium
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Creba J A
Downes C P
Hawkins P T
Brewster G
Michell R H
Kirk C J
References (89)
89 references, click to expand
  1. Stimulated inositol lipid metabolism: an introduction.
    Cell Calcium. 1982 Oct;3(4-5):285-94 PMID: 6297737
  2. De novo synthesis of glucokinase in hepatocytes isolated from neonatal rats.
    FEBS Lett. 1980 Feb 25;111(1):115-9 PMID: 6987080
  3. Inositol phospholipids and cell surface receptor function.
    Biochim Biophys Acta. 1975 Mar 25;415(1):81-47 PMID: 164246
  4. Effect of the alpha-agonist noradrenaline on total and 45Ca2+ movements in mitochondria of rat liver cells.
    Biochem J. 1981 Oct 15;200(1):177-80 PMID: 7332537
  5. Acetylcholine increases the breakdown of triphosphoinositide of rabbit iris muscle prelabelled with [32P] phosphate.
    Biochem J. 1977 Jan 15;162(1):61-73 PMID: 192213
  6. The influence of vasopressin and related peptides on glycogen phosphorylase activity and phosphatidylinositol metabolism in hepatocytes.
    Biochem J. 1979 Feb 15;178(2):493-6 PMID: 444224
  7. Relationship between phosphatidylinositol synthesis and recovery of 5-hydroxytryptamine-responsive Ca2+ flux in blowfly salivary glands.
    Biochem J. 1979 Jun 15;180(3):655-61 PMID: 486139
  8. Studies of receptor-stimulated inositol lipid metabolism should focus upon measurements of inositol lipid breakdown.
    Biochem J. 1981 Jul 15;198(1):247-8 PMID: 6275840
  9. Inhibitory action of guanosine 3', 5'-monophosphate on thrombin-induced phosphatidylinositol turnover and protein phosphorylation in human platelets.
    Biochem Biophys Res Commun. 1981 Jul 16;101(1):61-7 PMID: 6269550
  10. Calcium ion fluxes induced by the action of alpha-adrenergic agonists in perfused rat liver.
    Biochem J. 1982 Dec 15;208(3):619-30 PMID: 6131669
  11. Nature of the receptor-regulated calcium pool in the rat parotid gland.
    J Physiol. 1982 Oct;331:557-65 PMID: 6185669
  12. Effect of neomycin and ionophore A23189 on ATP levels and turnover of polyphosphoinositides in human erythrocytes.
    Can J Biochem. 1977 Sep;55(9):1007-12 PMID: 198069
  13. Increased formation of phosphatidic acid induced with vasopressin or Ca2+ ionophore A23187 in rat hepatocytes.
    Biochem Pharmacol. 1982 Aug 15;31(16):2663-7 PMID: 6814442
  14. Inositol lipids and cell stimulation in mammalian salivary gland.
    Cell Calcium. 1982 Oct;3(4-5):369-83 PMID: 6297740
  15. [1-beta-Mercapto-beta,beta-cyclopentamethylenepropionic acid),2-(O-methyl)tyrosine ]argine-vasopressin and [1-beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)]argine-vasopressine, two highly potent antagonists of the vasopressor response to arginine-vasopressin.
    J Med Chem. 1980 Apr;23(4):364-8 PMID: 6892930
  16. Calcium-activated hydrolysis of phosphatidyl-myo-inositol 4-phosphate and phosphatidyl-myo-inositol 4,5-bisphosphate in guinea-pig synaptosomes.
    Biochem J. 1978 Nov 15;176(2):541-52 PMID: 217364
  17. Is phosphatidylinositol now out of the calcium gate?
    Nature. 1982 Jan 28;295(5847):281-2 PMID: 6276765
  18. ON THE OCCURRENCE OF DIPHOSPHOINOSITOL IN THE LIPIDS OF LIVER AND PANCREAS.
    Biochim Biophys Acta. 1964 Aug 5;84:391-403 PMID: 14230813
  19. Effects of acetylcholine on the incorporation of (32P)orthophosphate in vitro into the phospholipids of subsynaptosomal, membranes from guinea-pig brain.
    J Neurochem. 1973 Jul;21(1):173-90 PMID: 4352757
  20. Increased phosphatidylinositol synthesis in rat embryo fibroblasts after growth stimulation and its inhibition by delta-hexachlorocyclohexane.
    Biochim Biophys Acta. 1980 May 28;618(2):282-92 PMID: 6155147
  21. Effects of quinine and apamin on the calcium-dependent potassium permeability of mammalian hepatocytes and red cells.
    J Physiol. 1981 Aug;317:67-90 PMID: 6273550
  22. The polyphosphoinositide phosphodiesterase of erythrocyte membranes.
    Biochem J. 1981 Jul 15;198(1):133-40 PMID: 6275838
  23. Influence of extracellular calcium ions on hormonal stimulation of glycogen breakdown in hepatocyte suspensions [proceedings].
    Biochem Soc Trans. 1977;5(4):992-4 PMID: 410684
  24. The inositol trisphosphate phosphomonoesterase of the human erythrocyte membrane.
    Biochem J. 1982 Apr 1;203(1):169-77 PMID: 6285891
  25. Phosphatidylinositol metabolism in rat hepatocytes stimulated by vasopressin.
    Biochem J. 1981 Jan 15;194(1):155-65 PMID: 7030316
  26. The action of insulin on the incorporation of [32P]phosphate in the phospholipids of rat adipose tissue.
    Biochim Biophys Acta. 1966 Jun 1;116(3):477-81 PMID: 4289986
  27. Kinetic aspects of cycloheximide-induced reversal of adrenocorticotropin effects on steroidogenesis and adrenal phospholipids in vivo.
    Proc Natl Acad Sci U S A. 1980 Dec;77(12):7189-93 PMID: 6261246
  28. Stimulus-permeability coupling: role of calcium in the receptor regulation of membrane permeability.
    Pharmacol Rev. 1978 Jun;30(2):209-45 PMID: 224401
  29. Acetylcholine action: biochemical aspects.
    Science. 1969 Aug 29;165(3896):862-6 PMID: 4307914
  30. D-myoinositol 1:2-cyclic phosphate 2-phosphohydrolase.
    Biochem J. 1972 Mar;127(1):113-8 PMID: 4342209
  31. Recent hypotheses regarding the phosphatidylinositol effect.
    Life Sci. 1981 Sep 21;29(12):1183-94 PMID: 7029181
  32. Minireview. Phosphatidylinositol specific phospholipases C.
    Life Sci. 1982 Apr 19;30(16):1323-35 PMID: 7087667
  33. Degradation of phosphatidylinositol-4,5-bisphosphate is insensitive to CA2+ mobilization in stimulated platelets.
    Biochem Biophys Res Commun. 1982 Nov 16;109(1):217-22 PMID: 6297477
  34. THE CHROMATOGRAPHIC SEPARATION OF POLYPHOSPHOINOSITIDES AND STUDIES ON THEIR TURNOVER IN VARIOUS TISSUES.
    Biochim Biophys Acta. 1964 Oct 2;84:550-62 PMID: 14250493
  35. Adrenocorticotropin and adenosine 3',5'-monophosphate stimulate de novo synthesis of adrenal phosphatidic acid by a cycloheximide-sensitive, CA++-dependent mechanism.
    Endocrinology. 1981 Dec;109(6):1895-901 PMID: 6273120
  36. Phosphoinositides. 3. Enzymic hydrolysis of inositol-containing phospholipids.
    Biochem J. 1961 Apr;79:193-200 PMID: 13752435
  37. The site of diphosphoinositide synthesis in rat liver.
    Biochem Biophys Res Commun. 1965 Nov 22;21(4):333-8 PMID: 4286175
  38. Gamma-hexachlorocyclohexane inhibits the initiation of lymphocyte growth by phytohemagglutinin.
    Biochem Pharmacol. 1971 Sep;20(9):2515-8 PMID: 4126989
  39. Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands.
    Biochem J. 1982 Sep 15;206(3):587-95 PMID: 7150264
  40. The liver angiotensin receptor involved in the activation of glycogen phosphorylase.
    Biochem J. 1982 Dec 15;208(3):809-17 PMID: 6299280
  41. Phosphoinositides. 5. The inositol lipids of ox brain.
    Biochem J. 1963 Jul;88(1):125-31 PMID: 16749024
  42. Involvement of alpha noradrenergic receptors in mediation of brain polyphosphoinositides metabolism in vivo.
    J Pharmacol Exp Ther. 1982 Jul;222(1):209-14 PMID: 6283069
  43. Requirement for calcium ions in acetylcholine-stimulated phosphodiesteratic cleavage of phosphatidyl-myo-inositol 4,5-bisphosphate in rabbit iris smooth muscle.
    Biochem J. 1980 Dec 15;192(3):783-91 PMID: 6263262
  44. On the role of calcium as second messenger in liver for the hormonally induced activation of glycogen phosphorylase.
    Biochim Biophys Acta. 1977 Feb 28;496(2):448-57 PMID: 189844
  45. Role of calcium in the hormonal regulation of liver metabolism.
    Biochim Biophys Acta. 1981 Dec 30;639(3-4):243-95 PMID: 7039675
  46. Rapid decrease of phosphatidylinositol 4,5-bisphosphate in thrombin-stimulated platelets.
    J Biol Chem. 1982 Nov 10;257(21):12705-8 PMID: 6290478
  47. Phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate: lipids in search of a function.
    Cell Calcium. 1982 Oct;3(4-5):467-502 PMID: 6297743
  48. Receptor regulation of calcium release and calcium permeability in parotid gland cells.
    Philos Trans R Soc Lond B Biol Sci. 1981 Dec 18;296(1080):37-45 PMID: 6121344
  49. The influence of extracellular calcium concentration on the vasopressin-stimulated incorporation of inorganic phosphate into phosphatidylinositol in hepatocyte suspensions.
    Biochem Soc Trans. 1978;6(5):1031-3 PMID: 744313
  50. Phospholipids in synaptic function.
    J Neurochem. 1979 Jan;32(1):5-14 PMID: 759584
  51. Exchange characteristics of the noradrenaline-sensitive calcium store in vascular smooth muscle cells or rabbit ear artery.
    J Physiol. 1981 Aug;317:263-79 PMID: 7310734
  52. The extraction of inositol-containing phospholipids and phosphatidylcholine from Saccharomyces cerevisiae and Neurospora crassa.
    J Lipid Res. 1980 Mar;21(3):309-15 PMID: 6445928
  53. Concanavalin A receptors of the surface membrane of Crithidia fasciculata.
    Biochem Soc Trans. 1981 Feb;9(1):135-6 PMID: 7215644
  54. The role of calcium ion as a mediator of the effects of angiotensin II, catecholamines, and vasopressin on the phosphorylation and activity of enzymes in isolated hepatocytes.
    J Biol Chem. 1979 Aug 10;254(15):7147-56 PMID: 222757
  55. Molecular mechanisms involved in alpha-adrenergic responses.
    Mol Cell Endocrinol. 1981 Sep;23(3):233-64 PMID: 6269923
  56. Ligand-stimulated inositol lipid metabolism in the liver: relationship to receptor function.
    Cell Calcium. 1982 Oct;3(4-5):399-411 PMID: 6297741
  57. Angiotensin II and alpha-adrenergic agonists inhibit rat liver adenylate cyclase.
    J Biol Chem. 1981 Mar 25;256(6):2603-6 PMID: 6110657
  58. Cyclic GMP metabolism and involvement in biological regulation.
    Annu Rev Biochem. 1977;46:823-96 PMID: 20041
  59. Heterologous desensitization of the cyclic AMP-independent glycogenolytic response in rat liver cells.
    Biochem J. 1981 Dec 15;200(3):509-14 PMID: 6123310
  60. The effects of Ca2+ and Sr2+ on Ca2+-sensitive biochemical changes in human erythrocytes and their membranes.
    Biochem J. 1981 Sep 15;198(3):441-5 PMID: 6275846
  61. Human erythrocyte cytosol phosphatidyl-inositol-bisphosphate phosphatase.
    Biochim Biophys Acta. 1981 Oct 13;661(2):323-33 PMID: 6271223
  62. Extraction of polyphosphoinositides with neutral and acidified solvents. A comparison of guinea-pig brain and liver, and measurements of rat liver inositol compounds which are resistant to extraction.
    Biochim Biophys Acta. 1970 Jun 9;210(1):86-91 PMID: 4318456
  63. Phosphatidylinositol metabolism in rat hepatocytes stimulated by glycogenolytic hormones. Effects of angiotensin, vasopressin, adrenaline, ionophore A23187 and calcium-ion deprivation.
    Biochem J. 1979 Sep 15;182(3):661-8 PMID: 229824
  64. Stimulation of phosphatidylinositol turnover in various tissues by cholinergic and adrenergic agonists, by histamine and by caerulein.
    Biochem J. 1979 Sep 15;182(3):669-76 PMID: 42389
  65. Sodium nitroprusside and other smooth muscle-relaxants increase cyclic GMP levels in rat ductus deferens.
    Nature. 1977 Feb 24;265(5596):750-1 PMID: 193029
  66. 5-Hydroxytryptamine stimulation of phosphatidylinositol hydrolysis and calcium signalling in the blowfly salivary gland.
    Cell Calcium. 1982 Oct;3(4-5):385-97 PMID: 6891617
  67. The interaction of cyclic nucleotides and calcium in the control of cellular activity.
    Adv Cyclic Nucleotide Res. 1975;6:1-98 PMID: 171926
  68. [ON INCORPORATION OF P32-LABELLED PHOSPHATE INTO DI- AND TRIPHOSPHOINOSITIDE OF VARIOUS RAT ORGANS].
    Biochem Z. 1964 Jan 28;339:327-30 PMID: 14126712
  69. Calcium movements in in situ mitochondria following activation of alpha-adrenergic receptors in rat liver cells.
    FEBS Lett. 1980 Jun 30;115(2):243-6 PMID: 6249640
  70. Phosphatidylinositol metabolism in mast cells and neutrophils.
    Cell Calcium. 1982 Oct;3(4-5):337-49 PMID: 6186378
  71. Myo-inositol lipids.
    Vitam Horm. 1975;33:529-73 PMID: 180679
  72. (3H)-vasopressin binding to isolated rat hepatocytes and liver membranes: regulation by GTP and relation to glycogen phosphorylase activation.
    J Recept Res. 1980;1(2):137-68 PMID: 6271952
  73. Hepatic action of vasopressin: lack of a role for adenosine-3',5'-cyclic monophosphate.
    FEBS Lett. 1974 Oct 1;47(1):128-31 PMID: 4372084
  74. Characteristics of rat liver phosphatidylinositol kinase and its presence in the plasma membrane.
    Biochim Biophys Acta. 1967 Dec 5;144(3):649-58 PMID: 4294903
  75. The control by Ca2+ of the polyphosphoinositide phosphodiesterase and the Ca2+-pump ATPase in human erythrocytes.
    Biochem J. 1982 Jan 15;202(1):53-8 PMID: 6282272
  76. Receptor-mediated net breakdown of phosphatidylinositol 4,5-bisphosphate in parotid acinar cells.
    Biochem J. 1982 Sep 15;206(3):555-60 PMID: 6184051
  77. Stimulation of inorganic-phosphate incorporation into phosphatidylinositol in rat thoracic aorta mediated through V1-vasopressin receptors.
    Biochem J. 1981 Jan 15;194(1):167-72 PMID: 6272723
  78. Inhibition by gamma-hexachlorocyclohexane of acetylcholine-stimulated phosphatidylinositol synthesis in cerebral cortex slices and of phosphatidic acid-inositol transferase in cerebral cortex particulate fractions.
    J Neurochem. 1969 Apr;16(4):475-83 PMID: 4305829
  79. Vasopressin and epinephrine stimulation of phosphatidylinositol breakdown in the plasma membrane of rat hepatocytes.
    Life Sci. 1981 Nov 2;29(18):1905-12 PMID: 7311724
  80. Quantitative aspects of drug-receptor interactions. I. Ca2+ and cholinergic receptor activation in smooth muscle: a basic model for drug-receptor interactions.
    J Theor Biol. 1973 Jul;40(1):125-54 PMID: 4723547
  81. Effects of calcium-antagonistic drugs on the stimulation by carbamoylcholine and histamine of phosphatidylinositol turnover in longitudinal smooth muscle of guinea-pig ileum.
    Biochem J. 1976 Nov 15;160(2):163-9 PMID: 1008847
  82. Is phosphatidylinositol really out of the calcium gate?
    Nature. 1982 Apr 8;296(5857):492-3 PMID: 7070496
  83. Stimulation by vasopressin and alpha-catecholamines of phosphatidylinositol formation in isolated rat liver parenchymal cells.
    J Biol Chem. 1980 Mar 10;255(5):1938-44 PMID: 6766458
  84. Enhanced phosphatidylinositol labelling in rat parotid fragments exposed to alpha-adrenergic stimulation.
    Biochem J. 1974 Jan;138(1):47-52 PMID: 4365258
  85. Phosphatidylinositol hydrolysis: a multifunctional transducing mechanism.
    Mol Cell Endocrinol. 1981 Nov;24(2):115-40 PMID: 6117490
  86. Evidence for the inhibitory role of guanosine 3', 5'-monophosphate in ADP-induced human platelet aggregation in the presence of nitric oxide and related vasodilators.
    Blood. 1981 May;57(5):946-55 PMID: 6111365
  87. Acetylcholine-stimulated phosphodiesteratic cleavage of phosphoinositides: hypothetical role in membrane depolarization.
    Ann N Y Acad Sci. 1969 Oct 17;165(2):743-54 PMID: 4310384
  88. The stimulation of inositol lipid metabolism that accompanies calcium mobilization in stimulated cells: defined characteristics and unanswered questions.
    Philos Trans R Soc Lond B Biol Sci. 1981 Dec 18;296(1080):123-38 PMID: 6121338
  89. Analysis of Ca2+ fluxes and Ca2+ pools in pancreatic acini.
    Philos Trans R Soc Lond B Biol Sci. 1981 Dec 18;296(1080):105-13 PMID: 6121336
Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2120733
Published
1983-06-15
Pages
733-47
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1153150
Subset
IM
External Links
PubMed source DOI: 10.1042/bj2120733 PMC Full Text View journal details
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