Regulation of Phosphoinositide Breakdown

  • John H. Exton
Part of the New Horizons in Therapeutics book series (NHTH)


Many hormones, neurotransmitters, and other molecules involved in intercellular communication exert their biological actions by activating a phospholipase C that catalyzes the breakdown of a specific phospholipid (phosphatidylinositol 4,5-bisphosphate or PIP2) in the plasma membrane of their target cells. The breakdown of PIP2 yields inositol 1,4,5-trisphosphate (IP3), which enters the cytosol, and 1,2-diacylglycerol (DAG), which remains in the membrane. IP3 has a second messenger role in that it rapidly releases Ca2+ ions from components of the endoplasmic reticulum, causing a rise in cytosolic Ca2+. This rise is responsible for many of the physiological responses observed, through the mediation of calmodulin and other Ca2+ - binding proteins (Fig. 1). DAG is also a second messenger because it activates the Ca2+-phospholipid-dependent protein kinase C. This phosphorylates a number of cellular proteins contributing to the responses (Fig. 1).


Phosphatidic Acid Guanine Nucleotide Pertussis Toxin Inositol Phosphate Liver Plasma Membrane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abdel-Latif, A. A., Akhtar, R. A., and Hawthorne, J. N., 1977, Acetylcholine increases the breakdown of triphosphoinositide of rabbit iris muscle prelabelled with [32p]phosphate, Biochem. J. 162:61–73.PubMedGoogle Scholar
  2. Agranoff, B. W., Murthy, P., and Sequin, E. B., 1983, Thrombin-induced phosphodiesteratic cleavage of phosphatidylinositol bisphosphate in human platelets. J. Biol. Chem. 258:2076–2078.PubMedGoogle Scholar
  3. Akhtar, R. A., and Abdel-Latif, A. A., 1984, Carbachol causes rapid phosphodiesteratic cleavage of phosphatidylinositol 4,5-bisphosphate and accumulation of inositol phosphates in rabbit iris smooth muscle; prazosin inhibits noradrenaline-and ionophore A23187-stimulated accumulation of inositol phosphates, Biochem. J. 224:291–300.PubMedGoogle Scholar
  4. Ambler, S. K., Brown, R. D., and Taylor, P., 1984, The relationship between phosphoinositol metabolism and mobilization of intracellular calcium elicited by alpha,-adrenergic receptor stimulation in BC3H-1 muscle cells, Mol. Pharmacol. 26:405–413.PubMedGoogle Scholar
  5. Amitai, G., Brown, R. D., and Taylor, P., 1984, The relationship between a1-adrenergic receptor occupation and the mobilization of intracellular calcium, J. Biol. Chem. 259:12519–12527.PubMedGoogle Scholar
  6. Aub, D. L., and Putney, J. W., Jr., 1984, Metabolism of inositol phosphates in parotid cells: Implications for the pathway of the phosphoinositide effect and for the possible messenger role of inositol trisphosphate, Life Sci. 34:1347–1355.PubMedGoogle Scholar
  7. Aub, D. L., and Putney, J. W., Jr., 1985, Properties of receptor-controlled inositol trisphosphate formation in parotid acinar cells, Biochem. J. 225:263–266.PubMedGoogle Scholar
  8. Aub, D. L., Frey, E. A., Sekura, R. D., and Cote, T. E., 1986, Coupling of the thyrotropinreleasing hormone receptor to phospholipase C by a GTP-binding protein distinct from the inhibitory or stimulatory GTP-binding protein, J. Biol. Chem. 261:9333–9340.PubMedGoogle Scholar
  9. Authi, K. S., and Crawford, N., 1985, Inositol 1,4,5-trisphosphate-induced release of sequestered Cat± from highly purified human platelet intracellular membranes, Biochem. J. 250:247–253.Google Scholar
  10. Baldassare, J. J., and Fisher, G. J., 1986a, Regulation of membrane associated and cytosolic phospholipase C activities in human platelets by guanosine triphosphate, J. Biol. Chem. 261:11942–11944.Google Scholar
  11. Baldassare, J. J., and Fisher, G. J., 1986b, GTP and cytosol stimulate phosphoinositide hydro- lysis in isolated platelet membranes, Biochem. Biophys. Res. Commun. 137:801–805.Google Scholar
  12. Banno, Y., Nakashima, S., and Nozawa, Y., 1986a, Partial purification of phosphoinositide phospholipase C from human platelet cytosol: Characterization of its three forms, Biochem. Biophys. Res. Commun. 136:713–721.Google Scholar
  13. Banno, Y., Nakashima, S., Tohmatsu, T., Nozawa, Y., and Lapetina, E. G., 1986b, GTP and GDP will stimulate platelet cytosolic phospholipase C independently of Cat+, Biochem. Biophys. Res. Commun. 140:728–734.Google Scholar
  14. Batty, I. R., Nahorski, S. R., and Irvine, R. F., 1985, Rapid formation of inositol (1,3,4,5) tetrakisphosphate following muscarinic receptor stimulation of rat cerebral corticol slices, Biochem. J. 232:211–215.PubMedGoogle Scholar
  15. Baudiere, B., Guillon, G., Bali, J.-P., and Jard, S., 1986. Muscarinic stimulation of inositol phosphate accumulation and acid secretion in gastric fundic mucosal cells, FEBS Lett. 198:321–325.PubMedGoogle Scholar
  16. Baukal, A. J., Guillemette, G., Rubin, R., Spat, A., and Catt, K. J., 1985, Binding sites for inositol trisphosphate in the bovine adrenal cortex, Biochem. Biophys. Res. Commun. 133:532–538.PubMedGoogle Scholar
  17. Berridge, M. J., 1983, Rapid accumulation of inositol trisphosphate reveals that agonists hydrolyse polyphosphoinositides instead of phosphatidylinositol, Biochem. J. 212:849–858.PubMedGoogle Scholar
  18. Berridge, M. J., 1984, Inositol trisphosphate and diacylglycerol as second messengers, Biochem. J. 220:345–360.PubMedGoogle Scholar
  19. Berridge, M. J., 1986, Intracellular signaling through inositol trisphosphate and diacylglycerol, Hoppe Seylers Z. Physiol. Chem. 367:447–456.Google Scholar
  20. Berridge, M. J., and Dawson, R. M. C., Downes, C. P., Heslop, J. P., and Irvine, R. F., 1983, Changes in the levels of inositol phosphates after agonist-dependent hydrolysis of membrane phosphoinositides, Biochem. J. 212:473–482.PubMedGoogle Scholar
  21. Berridge, M. J., Heslop, J. P., Irvine, R. F., and Brown, K. D., 1984, Inositol trisphosphate formation and calcium mobilization in Swiss 3T3 cells in response to platelet-derived growth factor, Biochem. J. 222:195–201.PubMedGoogle Scholar
  22. Besterman, J. M., Watson, S. P., and Cuatrecasas, P., 1986, Lack of association of epidermal growth factor-, insulin-and serum-induced mitogenesis with stimulation of phosphoinositide degradation in BALB/c 3T3 fibroblasts, J. Biol. Chem. 261:723–727.PubMedGoogle Scholar
  23. Biden, T. J., and Wollheim, C. B., 1986, Cat+ regulates the inositol tris/tetrakisphosphate pathway in intact and broken preparations of insulin-secreting R1Nm5F cells, J. Biol. Chem. 261:11931–11934.PubMedGoogle Scholar
  24. Biden, T. J., Prentki, M., Irvine, R. F., Berridge, M. J., and Wollheim, C. B., 1984, Inositol 1,4,5-trisphosphate mobilizes intracellular Cat+ from permeabilized insulin-secreting cells, Biochem. J. 223:467–473.PubMedGoogle Scholar
  25. Biden, T. J., Wollheim, C. B., and Schlegel, W., 1986, Inositol 1,4,5-trisphosphate and intracellular Cat+ homeostasis in clonal pituitary cells, J. Biol. Chem. 261:7223–7229PubMedGoogle Scholar
  26. Billah, M. M., and Lapetina, E. G., 1982, Rapid decrease of phosphatidylinositol 4,5-bi-sphosphate in thrombin-stimulated platelets, J. Biol. Chem. 257:12705–12708.PubMedGoogle Scholar
  27. Billah, M. M., and Michell, R. H., 1979, Phosphatidylinositol metabolism in rat hepatocytes stimulated by glycogenolytic hormones, Biochem. J. 182:661–668.PubMedGoogle Scholar
  28. Blackmore, P. F., Bocckino, S. B., Waynick, L. E., and Exton, J. H., 1985, Role of a guanine nucleotide-binding regulatory protein in the hydrolysis of hepatocyte phosphatidylinositol 4,5-bisphospate by calcium-mobilizing hormones and the control of cell calcium. Studies utilizing aluminum fluoride. J. Biol. Chem. 260:14477–14483.PubMedGoogle Scholar
  29. Boer, R., and Fahrenholz, F., 1985, Photoaffinity labeling of the V1 vasopressin receptor in plasma membranes from rat liver, J. Biol. Chem. 260:15051–15054.PubMedGoogle Scholar
  30. Bojanic, D., and Fain, J. N., 1986, Guanine nucleotide regulation of [3H]vasopressin binding to liver plasma membranes solubilized receptors. Evidence for the involvement of a guanine nucleotide regulatory protein, Biochem. J. 240:361–365.PubMedGoogle Scholar
  31. Bokoch, G. M., and Gilman, A. G., 1984, Inhibition of receptor-mediated release of arachidonic acid by pertussis toxin, Cell 39:301–308.PubMedGoogle Scholar
  32. Bosch, F., Bouscarel, B., Slaton, J., Blackmore, P. F., and Exton, J. H., 1986, Epidermal growth factor mimics insulin effects in rat hepatocytes, Biochem. J. 239:523–530.PubMedGoogle Scholar
  33. Boyer, J. L., Garcia, A., Posadas, C., and Garcia-Sainz, J. A., 1984, Differential effect of pertussis toxin on the affinity state for agonists of renal a1- and a2-adrenoceptors, J. Biol. Chem. 259:8076–8079.PubMedGoogle Scholar
  34. Brass, L. F., and Joseph, S. K., 1985, A role for inositol trisphosphate in intracellular Ca2+ mobilization and granule secretion in platelets, J. Biol. Chem. 260:15172–15179.PubMedGoogle Scholar
  35. Brass, L. F., Laposata, M., Banga, H. S., and Rittenhouse, S. E., 1986, Regulation of the phosphoinositide hydrolysis pathway in thrombin-stimulated platelets by a pertussis toxin-sensitive guanine nucleotide-binding protein, J. Biol. Chem. 261:16838–16847.PubMedGoogle Scholar
  36. Brown, J. E.. and Rubin, L. J., 1984. A direct demonstration that inositol trisphosphate induces an increase in intracellular calcium in Limulus photoreceptors, Biochem. Biophys. Res. Commun. 125:1137–1142.PubMedGoogle Scholar
  37. Brown, J. E., Rubin, L. J., Ghalayini, A. J., Tarver, A. P., Irvine, R. F., Berridge, M. J., and Anderson, R. E.. 1984, myo-Inositol polyphosphate may be a messenger for visual excitation in Limulus photoreceptors, Nature 311:160–163.PubMedGoogle Scholar
  38. Burgess, G. M., Godfrey, P. P., McKinney, J. S., Berridge, M. J., Irvine, R. F., and Putney, J. W., Jr., 1984a, The second messenger linking receptor activation to internal Ca release in liver, Nature 309:63–66.Google Scholar
  39. Burgess, G. M., Irvine, R. F., Berridge, M. J., McKinney, J. S., and Putney, J. W.. Jr.. 1984b, Actions of inositol phosphates on Cat - pools in guinea-pig hepatocytes, Biochem. J. 224:741–746.Google Scholar
  40. Burgess, G. M., McKinney, J. S., Irvine, R. F., Berridge, M. J., Hoyle, P. C.. and Putney, J. W., Jr., 1984c, Inositol, 1,4,5-trisphosphate may be a signal for f-Met-Leu-Phe-induced intracellar calcium mobilization in human leucocytes (HL-60 cells). FEBS Lea. 176:193–196.Google Scholar
  41. Busa, W. B., Ferguson, J. E., Joseph, S. K., Williamson, J. R., and Nuccitelli, R., 1985, Activation of frog (Xenopus laevis) eggs by inositol trisphosphate. I. Characterization of Cat’ release from intracellular stores, J. Cell Biol. 101:677–682.PubMedGoogle Scholar
  42. Bylund, D. B.. and U’Prichard, D. C., 1983, Characterization of au-and a,-adrenergic receptors. Int. Rev. Neurobiol. 24:343–431.PubMedGoogle Scholar
  43. Canessa de Scarnatti, O., and Lapetina, E., 1974, Adrenergic stimulation of phosphatidylinositol labelling in rat vas deferens, Biochim. Biophys. Acta 360:298–305.Google Scholar
  44. Capponi, A. M., and Catt, K. J., 1980, Solubilization and characterization of adrenal and uterine angiotensin II receptors after photoaffinity labeling, J. Biol. Chem. 255:12081–12086.PubMedGoogle Scholar
  45. Charest, R., Prpic, V., Exton, J. H., and Blackmore, P. F., 1985, Stimulation of inositol trisphosphate formation in hepatocytes by vasopressin, epinephrine and angiotensin II and its relationship to changes in cytosolic free Cat+, Biochem. J. 227:79–90.PubMedGoogle Scholar
  46. Chau, L.-Y., and Tai, H.-H., 1982, Resolution into two different forms and study of the properties of phosphatidylinositol-specific phospholipase C from human platelet cytosol, Biochim. Biophys. Acta 713:344–351.PubMedGoogle Scholar
  47. Chueh, S.-H., and Gill, D. L., 1986, Inositol 1,4,5-trisphosphate and guanine nucleotides activate calcium release from endoplasmic reticulum via distinct mechanisms, J. Biol. Chem. 261:13883–13886.PubMedGoogle Scholar
  48. Cockroft, S., and Gomperts, B. D., 1985, Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase, Nature 314:534–536.Google Scholar
  49. Conn, P. J., and Sanders-Bush, E., 1985, Serotonin stimulated phosphoinositide turnover: Mediation by the S2 binding site in rat cerebral cortex but not in subcortical regions, J. Pharmacol. Exp. Ther. 234:195–203.PubMedGoogle Scholar
  50. Connolly, T. M., Bross, T. E., and Majerus, P. W., 1985, Isolation of a phosphomonoesterase from human platelets that specifically hydrolyzes the 5-phosphate of inositol 1,4,5-trisphosphate, J. Biol. Chem. 260:7868–7874.PubMedGoogle Scholar
  51. Connolly, T. M., Lawing, W. J., Jr., and Majerus, P. W., 1986, Protein kinase C phosphorylates human platelet inositol trisphosphate 5’-phosphomonoesterase increasing the phosphatase activity, Cell 49:951–958.Google Scholar
  52. Connolly, T. M., Bansal, V. S., Bross, T. E., Irvine, R. F., and Majerus, P. W., 1987, The metabolism of the tris-and tetraphosphates of inositol by 5-phosphomonoesterase and 3-kinase enzymes, J. Biol. Chem. 262:2146–2149.PubMedGoogle Scholar
  53. Creba, J. A., Downes, C. P. K., Hawkins, P. T., Brewster, G., Michell, R. H., and Kirk, C. J., 1983, Rapid breakdown of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in rat hepatocytes stimulated by vasopressin and other Cat+-mobilizing hormones, Biochem. J. 212:733–747.PubMedGoogle Scholar
  54. Dawson, A. P., and Irvine, R. F., 1984, Inositol (1,4,5)trisphosphate-promoted Cat+ release from microsomal fractions of rat liver, Biochem. Biophys. Res. Commun. 120:858–864.PubMedGoogle Scholar
  55. Chaffoy de Courcelles, D., Leysen, J. E., De Clerck, F., Van Belle, H., and Janssen, P. A. J., 1985, Evidence that phospholipid turnover is the signal transducing system coupled to the serotonin-S2 receptor sites, J. Biol. Chem. 260:7603–7608.PubMedGoogle Scholar
  56. Deckmyn, H., Tu, S.-M., and Majerus, P. W., 1986, Guanine nucleotides stimulate soluble phosphoinositide-specific phospholipase C in the absence of membranes, J. Biol. Chem. 261:16553–16558.PubMedGoogle Scholar
  57. Delfert, D. M., Hill, S., Pershadsingh, H. A., Sherman, W. R., and McDonald, J. M., 1986, myolnositol 1,4,5-trisphosphate mobilizes Cat+ from isolated adipocyte endoplasmic reticulum but not from plasma membranes, Biochem. J. 236:37–44.PubMedGoogle Scholar
  58. De Torrontegui, G., and Berthet, J., 1966, The action of insulin on the incorporations of [32p]phosphate in the phospholipids of rat adipose tissue, Biochim. Biophys. Acta 116:477–481.PubMedGoogle Scholar
  59. Dougherty, R. W., Godfrey, P. P., Hoyle, P. C., Putney, J. W., Jr., and Freer, R. J., 1984, Secretagogue-induced phosphoinositide metabolism in human leucocytes, Biochem. J. 222:307–314.PubMedGoogle Scholar
  60. Downes, C. P., and Wusteman, M. M., 1983, Breakdown of polyphosphoinositides and not phosphatidylinositol accounts for muscarinic agonist-stimulated inositol phospholipid metabolism in rat parotid glands, Biochem. J. 216:633–640.PubMedGoogle Scholar
  61. Downes, C. P., Mussat, M. C., and Michell, R. H., 1982, The inositol trisphosphate phosphomonoesterase of the human erythrocyte membrane, Biochem. J. 203:169–177.PubMedGoogle Scholar
  62. Downes, C. P., Hawkins, P. T., and Irvine, R. F., 1986, Inositol 1,3,4,5-tetrakisphosphate is the probable precursor of inositol 1,3,4-trisphosphate in agonist-stimulated parotid gland, Biochem. J. 238:501–506.PubMedGoogle Scholar
  63. Ebstein, R. P., Bennett, E. R., Stessman, J., and Lerer, B., 1987, Isoelectric focusing of human platelet phospholipase C: Evidence for multimolecular forms, Life Sci. 40:161–167.PubMedGoogle Scholar
  64. El-Refai, M. F., Blackmore, P. F., and Exton, J. H., 1979, Evidence for two a-adrenergic binding sites in liver plasma membranes. Studies with [3H]epinephrine and [3H]dihydroergocryptine, J. Biol. Chem. 254:4375–4386.PubMedGoogle Scholar
  65. Enjalbert, A., Sladeczek, F., Guillon, G., Bertrand, P., Shu, C., Epelbaum, J., Garcia-Sainz, A., Jard, S., Lombard, C., Kordon, C., and Bockaert, J., 1986, Angiotensin II and dopamine modulate both cAMP and inositol phosphate production in anterior pituitary cells, J. Biol. Chem. 261:4071–4075.PubMedGoogle Scholar
  66. Exton, J. H., 1987, Mechanisms of a1-adrenergic and related responses: Roles of calcium, phosphoinositides, guanine nucleotides, diacylglycerol, calmodulin and changes in protein phosphorylation, in: Cell Membranes: Methods and Reviews (E. L. Elson, W. A. Frazier, and L. Glaser, eds.), Plenum Press, New York.Google Scholar
  67. Fahrenholz, F., Kojro, E., Muller, M., Boer, R., Lohr, R., and Grzonka, Z., 1986, Iodinated photoreactive vasopressin antagonists: Labelling of hepatic vasopressin receptor subunits, Eur. J. Biochem. 161:321–328.PubMedGoogle Scholar
  68. Farese, R. V., Larson, R. E., and Sabir, M. A., 1982, Insulin acutely increases phospholipids in the phosphatidate—inositide cycle in rat adipose tissue, J. Biol. Chem. 257:4042–4045.PubMedGoogle Scholar
  69. Farese, R. V., Barnes, D. E., Davis, J. S., Standaert, M. L., and Pollet, R. J., 1984, Effects of insulin and protein synthesis inhibitors on phospholipid metabolism, diacylglycerol levels, and pyruvate dehydrogenase activity in BC3–1H cultured myocytes, J. Biol. Chem. 259:7094–7100.PubMedGoogle Scholar
  70. Farese, R. V., Davis, J. S., Barnes, D. E., Standaert, M. L., Babischkin, J. S., Hoek, R., Rosie, N. K., and Pollet, R. J., 1985, The de novo phospholipid effect of insulin is associated with increases in diacylglycerol, but not inositol phosphate or cytosolic Cat’, Biochem. J. 231:269–279.PubMedGoogle Scholar
  71. Farese, R. V., Kuo, J. Y., Babischkin, J. S., and Davis, J. S., 1986, Insulin provokes a transient activation of phospholipase C in the rat epididymal fat pad, J. Biol. Chem. 261:8589–8592.PubMedGoogle Scholar
  72. Fein, A., Payne, R., Corson, D. W., Berridge, M. J., and Irvine, R. F., 1984, Photoreceptor excitation and adaptation by inositol I,4,5-trisphosphate, Nature 311:157–160.Google Scholar
  73. Fischer, S., Fagard, R., Comoglio, P., and Gacon, G.. 1985, Phosphoinositides are not phosphorylated by the very active tyrosine protein kinase from murine lymphoma LSTRA, Biochem. Biophys. Res. Commun. 132:481–489.PubMedGoogle Scholar
  74. Fisher, S. K., 1986. Inositol lipids and signal transduction at CNS muscarinic receptor, Trends Pharmacol. Sci. 7:(Suppl.)61–65.Google Scholar
  75. Fitzgerald, T. J., Uhing, R. J., and Exton, J. H., 1986, Solubilization of the vasopressin receptor from liver plasma membranes. Evidence for a receptor—GTP—binding protein complex, J. Biol. Chem. 261:16871–16877.PubMedGoogle Scholar
  76. Gallo-Payet, N., Guillon, G., Balestre, M. N., and Jard, S., 1986, Vasopressin induces breakdown of membrane phosphoinositides in adrenal glomerulosa and fasciculata cells, Endocrinology 119:1042–1047.PubMedGoogle Scholar
  77. Gershengorn, M. C., Geras, E., Purrello, V. S., and Rebecchi, M. J., 1984, Inositol trisphosphate mediates thyrotropin-releasing hormone mobilization of non-mitochondrial calcium in rat mammotropic pituitary cells, J. Biol. Chem. 259:10675–10681.PubMedGoogle Scholar
  78. Geynet, P., Borsodi, A., Ferry, N., and Hanoune, J., 1980, Proteolysis of rat liver plasma membranes cancels the guanine nucleotide sensitivity of agonist binding to the alpha-receptor, Biochem. Biophys. Res. Commun. 97:947–954.PubMedGoogle Scholar
  79. Gomperts, B. D., 1983. Involvement of guanine nucleotide-binding protein in the gating of Ca’ by receptors, Nature 306:64–66.PubMedGoogle Scholar
  80. Graham, R. M., Hess, H.-J., and Homcy, C. J., 1982, Biophysical characterization of the purified al-adrenergic receptor and identification of the hormone binding subunit. J. Biol. Chem. 257:15174–15181.PubMedGoogle Scholar
  81. Grandt, R., Greiner, C., Zubin, P., and Jakobs, K. H., 1986, Bradykinin stimulates GTP hydrolysis in NG108–15 membranes by a high-affinity, pertussis toxin-insensitive GTPase, FEBS Leu. 196:279–283.Google Scholar
  82. Guillemette, G., Balla, T., Baukal, A. J., Spat, A., and Catt, K. J., 1987, Intracellular receptors for inositol 1,4,5-trisphosphate in angiotensin II target tissues, J. Biol. Chem. 262:1010–1015.PubMedGoogle Scholar
  83. Guillon, G., Courand, P.-O., Butlen, D., Cantau, B., and Jard, S., 1980, Size of vasopressin receptors from rat liver and kidney, Eur. J. Biochem. 111:287–294.PubMedGoogle Scholar
  84. Habenicht, A. J. R., Glomset, J. A., King, W. C., Nist, C., Mitchell, C. D., and Ross, R., 1981, Early changes in phosphatidylinositol and arachidonic acid metabolism in quiescent Swiss 3T3 cells stimulated to divide by platelet-derived growth factor, J. Biol. Chem. 256:12329–12335.PubMedGoogle Scholar
  85. Hansen, C. A., Mah, S., and Williamson, J. R., 1986, Formation and metabolism of inositol 1,3,4,5-tetrakisphosphate in liver, J. Biol. Chem. 261:800–8103.Google Scholar
  86. Harden, T. K., Tanner, L. I., Martin, M. W., Nakahata, N., Hughes, A. R., Hepler, J. R., Evans, T., Masters, S. B., and Brown, J. H., 1986, Characteristics of two biochemical responses to stimulation of muscarinic cholinergic receptors, Trends Pharmacol. Sci. 7:(Suppl.)14–18.Google Scholar
  87. Harrington, C. A., and Eichberg, J., 1983, Norepinephrine causes a1-adrenergic receptor-mediated decrease of phosphoinositide in isolated rat liver plasma membranes supplementeed with cytosol, J. Biol. Chem. 258:2087–2090.PubMedGoogle Scholar
  88. Hasegawa-Sasaki, H., 1985, Early changes in inositol lipids and their metabolites induced by platelet-derived growth factor in quiescent Swiss mouse 3T3 cells, Biochem. J. 232:99109.Google Scholar
  89. Haslam, R. J., and Davidson, M. M. L., 1984a, Guanine nucleotides decrease the free [Ca2+] required for secretion of serotonin from permeabilized blood platelets. Evidence of a role for a GTP-binding protein in platelet activation, FEBS Lett. 174:90–95.Google Scholar
  90. Haslam, R. J., and Davidson, M. M. L., 1984b, Receptor-induced diacylglycerol formation in permeabilized platelets; possible role for a GTP-binding protein, J. Receptor Res. 4:605–629.Google Scholar
  91. Henne, V., and Soling, H.-D., 1986, Guanosine 5’-triphosphate releases calcium from rat liver and guinea pig parotid gland endoplasmic reticulum independently of inositol 1,4,5-trisphosphate, FEBS Lett. 202:267–273.PubMedGoogle Scholar
  92. Hepler, J. R., and Harden, T. K., 1986, Guanine nucleotide-dependent pertussis toxin-insensitive stimulation of inositol phosphate formation by carbachol in a membrane preparation from human astrocytoma cells. Biochem. J. 239:141–146.PubMedGoogle Scholar
  93. Hepler, J. R., Nakahata, N., Lovenberg, T. W., DiGuiseppi, J., Herman, B., Earp, H. S., and Harden, T. K., 1987, Epidermal growth factor stimulates the rapid accumulation of inositol (1,4,5)-trisphosphate and a rise in cytosolic calcium mobilized from intracellular stores in A431 cells, J. Biol. Chem. 262:2951–2956.PubMedGoogle Scholar
  94. Heslop, J. P., Blakeley, D. M., Brown, K. D., Irvine, R. F., and Berridge, M. J., 1986, Effects of bombesin and insulin on inositol (1,4,5)trisphosphate and inositol (1,3,4)trisphosphate formation in Swiss 3T3 cells, Cell 47:703–709.PubMedGoogle Scholar
  95. Higashida, H., and Brown, D. A., 1986, Membrane current responses to intracellular injections of inositol 1,3,4,5-tetrakisphosphate and inositol 1,3,4-trisphosphate in GN108–15 hybrid cells, FEBS Lett. 208:283–286.PubMedGoogle Scholar
  96. Higashida, H., Streaty, R. A., Klee, W., and Nirenberg, M., 1986, Bradykinin-activated transmembrane signals are coupled via No or Ni to production of inoisitol, 1,4,5-trisphosphate, a second messenger in NG108–15 neuroblastoma glioma hybrid cells, Proc. Natl. Acad. Sci. U.S.A. 83:942–946.PubMedGoogle Scholar
  97. Hinkle, P. M., and Phillips, W. J., 1984, Thyrotropin-releasing hormone stimulates GTP hydrolysis by membranes from GH4C1 rat pitutary tumor cells, Proc. Natl. Acad. Sci. U.S.A. 81:6183–6187.PubMedGoogle Scholar
  98. Hirasawa, K., Irvine, R. F., and Dawson, R. M. C., 1982, Heterogeneity of the calcium-dependent phosphatidylinositol phosphodiesterase of rat brain, Biochem. J. 205:437–442.PubMedGoogle Scholar
  99. Hirata, M., Kukita, M., Sasaguri, T., Suematsu, E., Hashimoto, T., and Koga, T., 1985, Increase in Ca2+ permeabilization of intracellular Ca2+ store membrane of saponintreated guinea pig peritoneal macrophages by inositol 1,4,5-trisphosphate, J. Biochem. 97:1575–1582.PubMedGoogle Scholar
  100. Hoffman, S. L., and Majerus, P. W., 1982, Identification and properties of two distinct phosphatidylinositol-specific phospholipase C enzymes from sheep seminal vesicles, J. Biol. Chem. 257:6461–6469.Google Scholar
  101. Holub, B. J., and Kuksis, A., 1978, Metabolism of molecular species of diacylglycerophospholipids, Adv. Lipid Res. 16:1–125.PubMedGoogle Scholar
  102. Honeyman, T. W., Strohsnitter, W., Scheid, C. R., and Schimmel, R. J., 1983, Phosphatidic acid and phosphatidylinositol labelling in adipose tissue, Biochem. J. 212:489–498PubMedGoogle Scholar
  103. Imai, A., and Gershengorn, M. C., 1987, Independent phosphatidylinositol synthesis in pituitary plasma membrane and endoplasmic reticulum, Nature 325:726–728.PubMedGoogle Scholar
  104. Imboden, J. B., and Stobo, J. D., 1985, Transmembrane signalling by the T cell antigen receptor, J. Exp. Med. 161:446–456.PubMedGoogle Scholar
  105. Irvine, R. F., and Moor, R. M., 1986, Microinjection of inositol 1,3,4,5-tetrakisphosphate activates sea urchin eggs by a mechanism dependent upon external Cat+, Biochem. J. 240:917–920.PubMedGoogle Scholar
  106. Irvine, R. F., Brown, K. D., and Berridge, M. J.. 1984a. Specificity of inositol trisphosphateinduced calcium release from permeabilized Swiss-mouse 3T3 cells. Biochem. J. 221:269–272.Google Scholar
  107. Irvine, R. F., Letcher, A. J.. and Dawson, R. M. C., 1984b, Phosphatidylinositol 4,5-bisphosphate phosphodiesterase and phosphomonoesterase activities of rat brain, Biochem. J. 218:177–185.Google Scholar
  108. Irvine, R. F., Letcher, A. J., Lander, D. J., and Downes, C. P., 1984c. Inositol trisphosphates in carbachol-stimulated rat parotid glands, Biochem. J. 223:237–243.Google Scholar
  109. Irvine, R. J., Anggard, E. E., Letcher, A. J., and Downes, C. P., 1985, Metabolism of inositol 1,4,5-trisphosphate and inositol 1,3.4-trisphosphate in rat parotid glands, Biochem. J. 229:505–511.PubMedGoogle Scholar
  110. Irvine, R. F., Letcher, A. J., Heslop, J. P., and Berridge, M. J., 1986a. The inositol tris/ tetrakisphosphate pathway—demonstration of Ins(1,4,5)P3 3-kinase activity in animal tissues, Nature 320:631–634.Google Scholar
  111. Irvine, R. F., Letcher, A. J., Lander, D. J.. and Berridge, M. J., 1986b, Specificity of inositol phosphate-stimulated Cat -’ mobilization from Swiss-mouse 3T3 cells, Biochem. J. 240:301–304.Google Scholar
  112. Ishii, H., Connolly, T. M., Bross, T. E., and Majerus, P. W., 1986, Inositol cyclic trisphosphate [inositol 1.2-(cyclic)-4,5-trisphosphate] is formed upon thrombin stimulation of human platelets, Proc. Natl. Acad. Sci. U.S.A. 83:6397–6401.PubMedGoogle Scholar
  113. Jackowski, S., Rettenmier, C. W., Sherr, C. J., and Rock, C. O., 1986, A guanine nucleotide-dependent phosphatidylinositol 4,5-diphosphate phospholipase C in cells transformed by the v fms and v-fes oncogenes, J. Biol. Chem. 261:4978–4985.PubMedGoogle Scholar
  114. Johnson, R. M., Connelly, P. A., Sisk, R. B., Pobiner, B. F., Hewlett, E. L., and Garrison, J. C., 1986, Pertussis toxin or phorbol 12-myristate 13-acetate can distinguish between growth factor-and angiotensin-stimulated signals in hepatocytes, Proc. Natl. Acad. Sci. U.S.A. 83:2032–2036.PubMedGoogle Scholar
  115. Jones, L. M., and Michell, R. H., 1978, Stimulus-response coupling at a-adrenergic receptors, Biochem. Soc. Trans. 6:673–688.PubMedGoogle Scholar
  116. Joseph, S. K., and Williams R. J.. 1985, Subcellular localization and some properties of the enzymes hydrolysing inositol polyphosphates in rat liver, FEBS LETT. 180:150–154.PubMedGoogle Scholar
  117. Joseph, S. K., and Williams, J. R., 1986, Characteristics of inositol trisphosphate-mediated Cat+ release from permeabilized hepatocytes, J. Biol. Chem. 261:14658–14664.PubMedGoogle Scholar
  118. Joseph, S. K., Thomas, A. P., Williams, R. J., Irvine, R. F., and Williamson, J. R., 1984a mvo-Inositol 1,4,5-trisphosphate: A second messenger for the hormonal mobilization of intracellular Cat-in liver, J. Biol. chem. 259:3077–3081.Google Scholar
  119. Joseph, S. K., Williamson, R. J., Corkey, B. E., Matschinsky, F. M., and Williamson, J. R., 1984b, The effect of inositol trisphosphate on Cat+ fluxes in insulin-secreting tumor cells, J. Biol. Chem. 259:12952–12955.Google Scholar
  120. Kanaho, Y., Moss, J., and Vaughan, M., 1985, Mechanism of inhibition of transducin GTPase activity by fluoride and aluminum. J. Biol. Chem. 260:11493–11497.PubMedGoogle Scholar
  121. Katada, T., Bokoch, G. M., Northup, J. K., Ui, M., and Gilman, A. G., 1984, The inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. Properties and function of the purified protein, J. Biol. Chem. 259:3568–3577.PubMedGoogle Scholar
  122. Kirk, C. J., Verrinder, T. R., and Hems, D. A., 1977, Rapid stimulation, by vasopressin and adrenaline, or inorganic phosphate incorporation into phosphatidylinositol in isolated hepatocytes, FEBS Lett. 83:267–271.PubMedGoogle Scholar
  123. Kirk, C. J., Creba, J. A., Downes, C. P., and Michell, R. H., 1981, Hormone-stimulated metabolism of inositol lipids and its relationship to hepatic receptor function, Biochem. Soc. Trans. 9:377–379.PubMedGoogle Scholar
  124. Kojima, I., Shibata, H., and Ogata, E., 1986, Pertussis toxin blocks angiotensin II-induced calcium influx but not inositol trisphosphate production in adrenal glomerulosa cells, FEBS Lett. 204:347–351.PubMedGoogle Scholar
  125. Lad, P. M., Olson, C. V., and Smiley, P. A., 1985, Association of the N-formyl-Met-Leu-Phe receptor in human neutrophils with a GTP-binding protein sensitive to pertussis toxin, Proc. Natl. Acad. Sci. U.S.A. 82:869–873.PubMedGoogle Scholar
  126. L’Allemain, G., and Pouyssegur, J., 1986, EGF and insulin action in fibroblasts, FEBS Lett. 197:344–348.PubMedGoogle Scholar
  127. Lambert, T. L., Kent, R. S., and Whorton, A. R., 1986, Bradykinin stimulation of inositol polyphosphate production in porcine aortic endothelial cells, J. Biol. Chem. 261:15288–15293.Google Scholar
  128. Leeb-Lundberg, L. M. F., Dickinson, K. E. J., Heald, S. L., Wikberg, J. E. S., Lefkowitz, R. J., and Caron, M. G., 1984, Photoaffinity labeling of mammalian a1-adrenergic receptors, J. Biol. Chem. 259:2579–2587.PubMedGoogle Scholar
  129. Leeb-Lundberg, L. M. F., Cotecchia, S., Lomasney, J. W., Debernadis, J. F., Lefkowitz, R. J., and Caron, M. G., 1985, Phorbol esters promote al-adrenergic receptor phosphorylation and receptor uncoupling from inositol phospholipid metabolism, Proc. Natl. Acad. Sci. U.S.A. 82:5651–5655.PubMedGoogle Scholar
  130. Lew, P. D., Monod, A., Krause, K.-H., Waldvogel, F. A., Biden, T. J., and Schlegel, W., 1986, The role of cytosolic free calcium in the generation of inositol 1,4,5-trisphosphate and inositol 1,3,4-trisphosphate in HL-60 cells, J. Biol. Chem. 261:13121–13127.PubMedGoogle Scholar
  131. Lin, S. H., and Fain, J. N., 1981, Vasopressin and epinephrine stimulation of phosphatidylinositol breakdown in the plasma membrane of rat hepatocytes, Life Sci. 29:1905–1912.PubMedGoogle Scholar
  132. Litosch, I., and Fain, J. N., 1985, 5-Methyltryptamine stimulates phospholipase C-mediated breakdown of exogenous phosphoinositides by blowfly salivary gland membranes, J. Biol. Chem. 260:16052–16055.PubMedGoogle Scholar
  133. Litosch, I., Lin, S. H., and Fain, J. N., 1983, Rapid changes in hepatocyte phosphoinositides induced by vasopressin, J. Biol. Chem. 258:13727–13732.PubMedGoogle Scholar
  134. Litosch, I., Wallis, C., and Fain, J. N., 1985, 5-Hydroxytryptamine stimulates inositol phosphate production in a cell-free system from blowfly salivary glands, J. Biol. Chem. 260:5464–5471.PubMedGoogle Scholar
  135. Lomasney, J. W., Leeb-Lundberg, L. M. F., Cotecchia, S., Regan, J. W., DeBernadis, J. F., Caron, M. G., and Lefkowitz, R. J., 1986, Mammalian a1-adrenergic receptor. Purification and characterization of the native receptor ligand binding subunit. J. Biol. Chem. 261:7710–7716.PubMedGoogle Scholar
  136. Low, M. G., Carroll, R. G., and Cox, A. C., 1986, Characterization of multiple forms of phosphoinositide-specific phospholipase C, purified from human platelets, Biochem. J. 237:139–145.PubMedGoogle Scholar
  137. Low, M. G., Carroll, R. C., and Weglicki, W. B. 1984, Multiple forms of phosphoinositidespecific phospholipase C of different relative molecular masses in animal tissues. Biochem. J. 221:813–820.PubMedGoogle Scholar
  138. Lucas, D. O., Bajjalich, S. M., Kowalchyk, J. A., and Martin, T. F. J., 1985, Direct stimulation by thyrotropin-releasing hormone of polyphosphoinositide hydrolysis in GH3 cell membranes by a guanine nucleotide-modulated mechanism, Biochem. Biophvs. Res. Commun. 132:721–728.Google Scholar
  139. Lynch, C. J., Blackmore, P. F., Charest, R., and Exton, J. H., 1985a, The relationships between receptor binding capacity for norepinephrine, angiotensin II and vasopressin and release of inositol trisphosphate. Cat mobilization and phosphorylase activation in rat liver, Mol. Pharmacol. 28:93–99.Google Scholar
  140. Lynch, C. J., Charest, R.. Blackmore, P. F., and Exton, J. H., 1985b, Studies on the hepatic a,-adrenergic receptor. Modulation of guanine nucleotide effects by calcium temperature and age, J. Biol. Chem. 260:1593–1600.Google Scholar
  141. Lynch, C. J., Sobo, G. E., and Exton, J. H.. 1986a, Studies on the hepatic a1-adrenergic receptor. An endogenous Cat--sensitive protease converts the a,-adrenergic receptor to a guanine nucleotide insensitive form, Biochem. Biophvs. Acta 885:110–120.Google Scholar
  142. Lynch, C. J., Prpic, V., Blackmore, P. F.. and Exton, J. H., 1986b, Effect of islet activating pertussis toxin on the binding characteristics of Ca---mobilizing hormones and on agonist activation of phosphorylase in hepatocytes, Mol. Pharmacol. 29:196–203.Google Scholar
  143. Macara, I. G.. 1986, Activation of °5Ca2 influx and 222Na`/H+ exchange by epidermal growth factor and vanadate in A431 cells is independent of phosphatidylinositol turnover and is inhibited by phorbol ester and diacylglycerol, J. Biol. Chem. 261:9321–9327.PubMedGoogle Scholar
  144. Macara, I. G., Marinetti, G. V. and Balduzzi, P. C., 1984, Transforming protein of avian sarcoma virus UR2 is associated with phosphatidylinositol kinase activity: Possible role in tumorigenesis, Proc. Natl. Acad. Sci. U.S.A. 81:2728–2732.PubMedGoogle Scholar
  145. MacDonald, M. L., Kuenzel, E. A., Glomset, J. A., and Krebs, E. G., 1985, Evidence from two transformed cell lines that the phosphorylations of peptide tyrosine and phosphatidylinositol are catalyzed by two different proteins, Proc. Natl. Acad. Sci. U.S.A. 82:3993–3997.PubMedGoogle Scholar
  146. MacDonald, M. L., Mack, K. F., and Glomset, J. A., 1987, Regulation of phosphoinositide phosphorylation in Swiss 3T3 cells stimulated by platelet-derived growth factor, J. Biol. Chem. 262:1105–1110.PubMedGoogle Scholar
  147. Machicao, E., and Wieland, O. H., 1984, Evidence that the insulin receptor-associated protein kinase acts as a phosphatidylinositol kinase, FEBS Lett. 175:113–116.PubMedGoogle Scholar
  148. Manning, D. R., Fraser, B. A., Kahn, R. A., and Gilman, A. G., 1984, ADP-ribosylation of transducin by islet-activating protein. Identification of asparagine as the site of ADPribosylation, J. Biol. Chem. 259:749–756.PubMedGoogle Scholar
  149. Martin, M. W., Evans, T., and Harden, T. K., 1985, Further evidence that muscarinic cholinergic receptors of 1321N1 astrocytoma cells couple to a guanine nucleotide regulatory protein that is not No Biochem. J. 229:539–544.PubMedGoogle Scholar
  150. Martin, T. F. J., 1983, Thyrotropin-releasing hormone rapidly activates the phosphodiesterase hydrolysis of polyphosphoinositides in GH3 pituitary cells J. Biol. Chem. 258:14816–14822.Google Scholar
  151. Martin, T. F. J., Bajjalieh, S. M., Lucas, D. O., and Kowalchyk, J. A., 1986a, Thyrotropinreleasing hormone stimulation of polyphosphoinositide hydrolysis in GH3 cell membranes is GTP-dependent but insensitive to cholera or pertussis toxin, J. Biol. Chem. 261:10041–10049.Google Scholar
  152. Martin, T. F. J., Lucas, D. O., Bajjalieh, S. M., and Kowalchyk, J. A., 1986b, Thyrotropinreleasing hormone activates a Cat+-dependent polyphosphoinositide phosphodiesterase in permeable GH3 cells, J. Biol. Chem. 261:2918–2927.Google Scholar
  153. Masters, S. B., Martin, M. W., Harden, T. K., and Brown, J. H., 1985, Pertussis toxin does not inhibit muscarinic receptor-mediated phosphoinositide hydrolysis or calcium mobilization, Biochem. J. 227:933–937.PubMedGoogle Scholar
  154. Mauco, G., Chap, H., and Douste-Blazy, L., 1983, Platelet activating factor (PAF-acether) promotes an early degradation of phosphatidylinositol-4,5-bisphosphate in rabbit platelets, FEBS Lett. 153:361–365.PubMedGoogle Scholar
  155. Merritt, J. E., Taylor, C. W., Rubin, R. P., and Putney, J. W., Jr., 1986, Evidence suggesting that a novel guanine nucleotide regulatory protein couples receptors to phospholipase C in exocrine pancreas, Biochem. J. 236:337–343.PubMedGoogle Scholar
  156. Michell, R. H., 1975, Inositol phospholipids and cell surface receptor function, Biochim. Biophys. Acta 20:339–344.Google Scholar
  157. Michell, R. H., 1979, Inositol phospholipids in membrane function, Trends Biochem. Sci. June:128–131.Google Scholar
  158. Michell, R. H., Kirk, C. J., and Billah, M. M., 1979, Hormonal stimulation of phosphatidylinositol breakdown, with particular reference to the hepatic effects of vasopressin, Biochem. Soc. Trans. 7:861–865.PubMedGoogle Scholar
  159. Michell, R. H., Kirk, C. J., Jones, L. M., Downes, C. P., and Creba, J. A., 1981, Stimulation of inositol lipid metabolism that accompanies calcium mobilization in stimulated cells: Defined characteristics and unanswered questions, Philos. Trans. R. Soc. Lond. (Biol.) 296:123–138.Google Scholar
  160. Molina y Vedia, L. M., and Lapetina, E. G. 1986, Phorbol 12,13-dibutyrate and 1-oleyl-2acetyldiacylglycerol stimulate inositol trisphosphate dephosphorylation in human platelets, J. Biol. Chem. 261:10493–10495.PubMedGoogle Scholar
  161. Moolenaar, W. H., Tertoolen, L. G. J., and deLaat, S. W., 1984, Growth factors immediately raise cytoplasmic free Cat+ in human fibroblasts, J. Biol. Chem. 259:8066–8069.PubMedGoogle Scholar
  162. Moolenaar, W. H., Aerts, R. J., Tertoolen, L. G. J., and deLaat, S. W., 1986, The epidermal growth factor-induced calcium signal in A431 cells, J. Biol. Chem. 261:279–284.PubMedGoogle Scholar
  163. Morgan, N. G., Rumford, G. M., and Montague, W., 1985, Studies on the role of inositol trisphosphate in the regulation of insulin secretion from isolated rat islets of Langerhans, Biochem. J. 228:713–18.PubMedGoogle Scholar
  164. Muallem, S., Schoeffield, M., Pandol, S., and Sachs, G., 1985, Inositol trisphosphate modification of ion transport in rough endoplasmic reticulum, Proc. Natl. Acad. Sci. U.S.A. 82:4433–4437.PubMedGoogle Scholar
  165. Murayama, T., and Ui, M., 1985, Receptor-mediated inhibition of adenylate cyclase and stimulation of arachidonic acid release in 3T3 fibroblasts, J. Biol. Chem. 260:7226–7233.PubMedGoogle Scholar
  166. Nakamura, T., and Ui, M., 1983, Suppression of passive cutaneous anaphylaxis by pertussis toxin, an islet-activating protein, as a result of inhibition of histamine release from mast cells, Biochem. Pharmacol. 32:3435–3441.PubMedGoogle Scholar
  167. Nakamura, T., and Ui, M., 1985, Simultaneous inhibitions of inositol phospholipid breakdown, arachidonic acid release, and histamine secretion in mast cells by islet-activating protein, pertussis toxin, J. Biol. Chem. 260:3584–3593.PubMedGoogle Scholar
  168. Nakanishi, H., Nomura, H., Kikkawa, V., Kishimoto, A., and Nishizuka, Y., 1985, Rat brain and liver soluble phospholipase C: Resolution of two forms with different requirements for calcium, Biochem. Biophys. Res. Commun. 132:582–590.PubMedGoogle Scholar
  169. Nanberg, E., and Putney, J. W., Jr., 1986, a1-Adrenergic activation of brown adipocytes leads to an increased formation of inositol polyphosphates, FEBS Leu. 195:319–322.Google Scholar
  170. Nosek, T. M., Williams, M. F., Zeigler, S. T., and Godt, R. E., 1986, Inositol trisphosphate enhances calcium release in skinned cardiac and skeletal muscle, Am. J. Physiol. 250:C807–0811.PubMedGoogle Scholar
  171. Okajima, F., and Ui, M., 1984, ADP-Ribosylation of the specific membrane protein by islet-activating protein, pertussis toxin, associated with inhibition of a chemotactic peptide-induced arachidonate release in neutrophils, J. Biol. Chem. 259:13863–13871.PubMedGoogle Scholar
  172. Okajima, F., Katada, T., and Ui, M., 1985, Coupling of guanine nucleotide regulatory protein to chemotactic peptide receptors in neutrophil membranes and its uncoupling by islet-activating protein, pertussis toxin, J. Biol. Chem. 260:6761–6768.PubMedGoogle Scholar
  173. Orellano, S., Solski, P. A., and Brown, J. H., 1987, Guanosine 5’-O-(thiotriphosphate)- dependent inositol trisphosphate formation in membranes is inhibited by phorbol ester and protein kinase C, J. Biol. Chem. 262:1638–1643.Google Scholar
  174. Oron, Y., Dascal, N., Nadler, E., and Lupu, M., 1985, Inositol 1,4,5-trisphosphate mimics muscarinic response in Xenopus oocytes. Nature 313:141–143.PubMedGoogle Scholar
  175. O’Rourke, F. A., Halenda, S. P., Zavoico, G. B., and Feinstein, M. B., 1985, Inositol 1,4,5trisphosphate releases Cat from a Cat’-transporting membrane vesicle fraction derived from human platelets, J. Biol. Chem. 260:956–962.PubMedGoogle Scholar
  176. Paris, S., and Pouyssegur, J., 1987, Further evidence for a phospholipase C-coupled G protein in hamster fibroblasts, J. Biol. Chem. 262:1970–1976.Google Scholar
  177. Pennington, S. R., and Martin, B. R., 1985. Insulin-stimulated phosphoinositide metabolism in isolated fat cells. J. Biol. Chem. 260:11039–11045.PubMedGoogle Scholar
  178. Pfeilschifter, J., and Bauer, C., 1986, Pertussis toxin abolishes angiotensin II-induced phosphoinositide hydrolysis and prostaglandin synthesis in rat renal mesangial cells. Biochem. J. 236:289–294.PubMedGoogle Scholar
  179. Pike, L. J., and Eakes, A. T.. 1987, Epidermal growth factor stimulates the production of phosphatidylinositol monophosphate and the breakdown of polyphosphoinositides in A431 cells. J. Biol. Chem. 262:1644–1651.PubMedGoogle Scholar
  180. Prentki, M. M., Biden, T. J., Janjic, D., Irvine, R. F., Berridge, M. J., and Wollheim, C. B., 1984a, Rapid mobilization of Ca2— from rat insulinoma microsomes by inositol-1.4.5trisphosphate, Nature 309:562–564.Google Scholar
  181. Prentki, M., Wollheim, C. B., and Lew, P. D., 1984b, Cat— homeostasis in permeabilized human neutrophils. Characterization of Cat ’-sequestering pools and the action of inositol, 1,4.5-trisphosphate, J. Biol. Chem. 259:13777–13782.Google Scholar
  182. Prentki, M., Corkey, B. E., and Matschinsky, F. M.. 1985, Inositol 1,4,5-trisphosphate and the endoplasmic reticulum Cat’ cycle of a rat insulinoma cell line, J. Biol. Chem. 260:9185–9190.PubMedGoogle Scholar
  183. Prpic, V., Blackmore, P. F., and Exton, J. H., 1982, Phosphatidylinositol breakdown induced by vasopressin and epinephrine in hepatocytes is calcium-dependent, J. Biol. Chem. 257:11323–11331.PubMedGoogle Scholar
  184. Putney, J. W., Jr., Burgess, G. M., Halenda, S. P., McKinney, J. S., and Rubin, R. P., 1983, Effects of secretagogues on [32p]phosphatidylinositol 4,5-bisphosphate metabolism in the exocrine pancreas, Biochem. J. 212:483–488.PubMedGoogle Scholar
  185. Rebecchi, M. J., and Gershengorn, M. C., 1983, Thyroliberin stimulates rapid hydrolysis of phosphatidylinositol 4,5-bisphosphate by a phosphodiesterase in rat mammotropic pituitary cells, Biochem. J. 216:287–294.PubMedGoogle Scholar
  186. Rhodes, D., Prpic, V., Exton, J. H., and Blackmore, P. F., 1983, Stimulation of phosphatidylinositol 4,5-bisphosphate hydrolysis in hepatocytes by vasopressin, J. Biol. Chem. 258:2770–2773.PubMedGoogle Scholar
  187. Rittenhouse, S. E., 1983, Human platelets contain phospholipase C that hydrolyzes polyphosphoinositides, Proc. Natl. Acad. Sci. U.S.A. 80:5417–5420.PubMedGoogle Scholar
  188. Rittenhouse, S. E., and Sasson, J. P., 1985, Mass changes in myoinositol trisphosphate in human platelets stimulated by thrombin: Inhibitory effects of phorbol ester, J. Biol. Chem. 260:8657–8660.PubMedGoogle Scholar
  189. Rogers, T. B., 1984, High affinity angiotensin II receptors in myocardial sarcolemmal membranes, J. Biol. Chem. 259:8106–8114.PubMedGoogle Scholar
  190. Rubin, R. P., Godfrey, P. P., Chapman, D. A., and Putney, J. W., Jr., 1984, Secretagogueinduced formation of inositol phosphates in rat exocrine pancreas, Biochem. J. 219:655–659.PubMedGoogle Scholar
  191. Sakai, M., and Wells, W. W., 1986, Action of insulin on the subcellular metabolism of polyphosphoinositides in isolated rat hepatocytes, J. Biol. Chem. 261:10058–10062.PubMedGoogle Scholar
  192. Sawyer, S. T., and Cohen, S., 1981, Enhancement of calcium uptake and phosphatidylinositol turnover by epidermal growth factor in A-431 cells, Biochemistry 20:6280–6286.PubMedGoogle Scholar
  193. Schacht, J., and Agranoff, B. W., 1972, Effects of acetylcholine on labeling of phosphatidate and phosphoinositides by [32p]orthophosphate in nerve, J. Biol. Chem. 247:774–777.Google Scholar
  194. Schimmel, R. J., McCarthy, L., and Dzierzanowski, D., 1985, Effects of pertussis toxin treatment on metabolism in hamster brown adipocytes, Am. J. Physiol. 249:C456–C463.PubMedGoogle Scholar
  195. Seidman, C E, Hess, H. J., Homcy, C. J., and Graham, R. M., 1984, Photoaffinity labeling of the al-adrenergic receptor using an 125I-labeled aryl azide analogue of prazosin, Biochemistry 23:3765–3770.PubMedGoogle Scholar
  196. Sekar, M. C., Dixon, J. F., and Hokin, L. E., 1987, The formation of inositol 1,2-cyclic 4,5trisphosphate and inositol 1,2-cyclic 4-bisphosphate on stimulation of mouse pancreatic minilobules with carbamylcholine, J. Biol. Chem. 262:340–344.PubMedGoogle Scholar
  197. Sen, I., Jim, K. F., and Soffer, R. L., 1983, Solubilization and characterization of an angiotensin II binding protein from liver, Eur. J. Biochem. 136:41–49.PubMedGoogle Scholar
  198. Seyfred, M. A., and Wells, W. W., 1984, Subcellular site and mechanism of vasopressinstimulated hydrolysis of phosphoinositides in rat hepatocytes, J. Biol. Chem. 259:7666–7672.PubMedGoogle Scholar
  199. Seyfred, M. A., Farrell, L. E., and Wells, W. W., 1984, Characterization of D-myo-inositol 1,4,5-trisphosphate phosphatase in rat liver plasma membranes, J. Biol. Chem. 259:13204–13208.PubMedGoogle Scholar
  200. Shukla, S. D., 1982, Phosphatidylinositol specific phospholipases C, Life Sci. 30:1323–1335.PubMedGoogle Scholar
  201. Slack, B. E., Bell, J. E., and Benos, D. J., 1986, Inositol-1,4,5-trisphosphate injection mimics fertilization potentials in sea urchin eggs, Am. J. Physiol. 250:C340–C344.PubMedGoogle Scholar
  202. Smith, C. D., Lane, B. C., Kusaka, I., Verghese, M. W., and Snyderman, R., 1985, Chemoattractant receptor-induced hydrolysis of phosphatidylinositol 4,5-bisphosphate in human polymorphonuclear leukocyte membranes, J. Biol. Chem. 260:5875–5878.PubMedGoogle Scholar
  203. Smith, J. B., Smith, L., Brown, E. R., Barnes, D., Sabir, M. A., Davis, J. S., and Farese, R. V., 1984, Angiotensin II rapidly increases phosphatidate—phosphoinositide synthesis and phosphoinositide hydrolysis and mobilizes intracellular calcium in cultured arterial muscle cells, Proc. Natl. Acad. Sci. U.S.A. 81:7812–7816.PubMedGoogle Scholar
  204. Smith, J. B., Smith, L., and Higgins, B. L., 1985, Temperature and nucleotide dependence of calcium release by myoinositol 1,4,5-trisphosphate in cultured vascular smooth muscle cells, J. Biol. Chem. 260:14413–14416.PubMedGoogle Scholar
  205. Somlyo, A. V., Bond, M., Somlyo, A. P., and Scarpa, A., 1985b, Inositol trisphosphateinduced calcium release and contraction in vascular smooth muscle, Proc. Natl. Acad. Sci. U.S.A. 82:5231–5235.Google Scholar
  206. Spat, A., Fabiato, A., and Rubin, R. P., 1986, Binding of inositol trisphosphate by a liver microsomal fraction, Biochem. J. 223:929–932.Google Scholar
  207. Stein, J. M., and Hales, C. N., and 1974, The effect of insulin on3213 1 incorporation into rat fat cell phospholipids, Biochim. Biophys. Acta 337:41–49.PubMedGoogle Scholar
  208. Stemweis, P. C., and Gilman, A. G., 1982, Aluminum: A requirement for activation of the regulatory component of adenylate cyclase by fluoride, Proc. Natl. Acad. Sci. U.S.A. 79:4888–4891.Google Scholar
  209. Stemweis, P. C., and Robishaw, J. D., 1984, Isolation of two proteins with high affinity for guanine nucleotides from membranes of bovine brain, J. Biol. Chem. 259:13806–13813.Google Scholar
  210. Stewart, S. J., Prpic, V., Powers, F. S., Bocckino, S. B., Isaacks, R. E., and Exton, J. H., 1986, Perturbation of the human T-cell antigen receptor—T3 complex leads to the production of inositol tetrakisphosphate: Evidence for conversion from inositol trisphosphate, Proc. Natl. Acad. Sci. U.S.A. 83:6098–6102.PubMedGoogle Scholar
  211. Stoehr, S. J., Smolen, J. E., Holz, R. W., and Agranoff, B. W., 1986, Inositol trisphosphate mobilizes intracellular calcium in permeabilized adrenal chromaffin cells, J. Neurochem. 46:637–640.PubMedGoogle Scholar
  212. Storey, D. J., Shears, S. B., Kirk, C. J., and Michell, R. H., 1984, Stepwise enzymatic dephosphorylation of inositol 1,4,5-trisphosphate to inositol in liver, Nature 312:374–376.PubMedGoogle Scholar
  213. Straub, R. E., and Gershengorn, M. C., 1986, Thyrotropin-releasing hormone and GTP activate inositol trisphosphate formation in membranes isolated from rat pituitary cells, J. Biol. Chem. 261:2712–2717.PubMedGoogle Scholar
  214. Streb, H., Irvine, R. F., Berridge M. J., and Schultz, I., 1983. Release of Cat+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol 1,4,5-triphosphate, Nature 306:67–69.PubMedGoogle Scholar
  215. Streb, H., Bayerdorffer, E., Haase, W., Irvine, R. F., and Schulz, I., 1984, Effect of inositol-1,4,5-trisphosphate in isolated subcellular fractions of rat pancreas, J. Membr. Biol. 81:241–253.PubMedGoogle Scholar
  216. Streb, H., Heslop, J. P., Irvine, R. F., Schulz, I., and Berridge, M. J., 1985, Relationship between secretagogue-induced Cat-release and inositol polyphosphate production is permeabilized pancreatic acinar cells, J. Biol. Chem. 260:7309–7315.PubMedGoogle Scholar
  217. Strnad, C. F., Parente, J. E.. and Wong, K., 1986, Use of fluoride ion as a probe for the guanine nucleotide-binding protein involved in the phosphoinositide-dependent neutrophil transduction pathway, FEBS Lett. 206:20–24.PubMedGoogle Scholar
  218. Suematsu, E., Hirata, M., Hashimoto, T., and Kuriyama, H., 1984, Inositol 1,4,5-trisphosphate releases Cat from intracellular store sites in skinned single cells of porcine coronary artery, Biochem. Biophys. Res. Commun. 120:481–485.PubMedGoogle Scholar
  219. Sugimoto, Y., Whitman, M., Cantley, L. C., and Erikson, R. L., 1984, Evidence that the Rous sarcoma virus transforming gene product phosphorylates phosphatidylinositol and diacylglycerol, Proc. Natl. Acad. Sci. U.S.A. 81:2117–2121.PubMedGoogle Scholar
  220. Taylor, D., Uhing, R. J., Blackmore, P. F., Prpic, V., and Exton, J. H., 1985, Insulin and epidermal growth factor do not affect phosphoinositide metabolism in rat liver plasma membranes and hepatocytes, J. Biol. Chem. 260:2011–2014.PubMedGoogle Scholar
  221. Taylor, S., and Exton, J. H., 1987, Guanine nucleotide and hormone regulation of polyphosphoinositide specific phospholipase C activity of rat liver plasma membranes: Divalent cation and phospholipid requirements, Biochem. J. 248:791–799.PubMedGoogle Scholar
  222. Thevenod, F., Streb, H., Ullrich, K. J., and Schulz, I., 1986, Inositol trisphosphate releases Cat+ from a nonmitochondrial store site in permeabilized rat cortical kidney cells, Kidney Int. 29:695–702.Google Scholar
  223. Thieleczek, R., and Heilmeyer, L. M. G., Jr., 1986, Inositol 1,4,5-trisphosphate enhances Ca’-+-sensitivity of the contractile mechanism of chemically skinned rabbit skeletal muscle fibre, Biochem. Biophys. Res. Commun. 135:662–669.PubMedGoogle Scholar
  224. Thomas, A. P., Marks, J. S., Coll, K. E., and Williamson, J. R., 1983, Quantitation and early kinetics of inositol lipid changes induced by vasopressin in isolated and cultured hepatocytes, J. Biol. Chem. 258:5716–5725.PubMedGoogle Scholar
  225. Thomas, A. P., Alexander, J., and Williamson, J. R., 1984, Relationship between inositol polyphosphate production and the increase of cytosolic free Cat+ induced by vasopressin in isolated hepatocytes. J. Biol. Chem. 259:5574–5584.PubMedGoogle Scholar
  226. Thompson, D. M., Cochet, C., Chambaz, E. M., and Gill, G. N., 1985, Separation and characterization of a phosphatidylinositol kinase activity that copurifies with the epidermal growth factor receptor, J. Biol. Chem. 260:8824–8830.PubMedGoogle Scholar
  227. Tolbert, M. E. M., White, A. C., Aspry, K., Cutts, J., and Pain, J. N., 1980, Stimulation by vasopressin and a-catecholamines of phosphatidylinositol formation in isolated rat liver parenchymal cells, J. Biol. Chem. 255:1938–1944.PubMedGoogle Scholar
  228. Uchida, T., Ito, H., Baum, B. J., Roth, G. S., Filburn, C. R., and Sacktor, B., 1982, Alpha,-adrenergic stimulation of phosphatidylinositol—phosphatidic acid turnover in rat parotid cells, Mol. Pharmacol. 21:128–132.PubMedGoogle Scholar
  229. Uhing, R. J., Jiang, H., Prpic, V., and Exton, J. H., 1985, Regulation of a liver plasma membrane phosphoinositide phosphodiesterase by guanine nucleotides and calcium, FEBS Lett. 188:317–320.Google Scholar
  230. Uhing, R. J., Prpic, V., Jiang, H., and Exton, J. H., 1986, Hormone stimulated polyphosphoinositide breakdown in rat liver plasma membranes: Roles of guanine nucleotides and calcium, J. Biol. Chem. 261:2140–2146.PubMedGoogle Scholar
  231. Van Dop, C., Yamanaka, G., Steinberg, F., Sekura, R. D., Manclark, C. R., Stryer, L., and Bourne, H. R., 1984, ADP-ribosylation of transducin by pertussis toxin blocks the light-stimulated hydrolysis of GTP and cGMP in retinal photoreceptors, J. Biol. Chem. 259:2326.Google Scholar
  232. Venter, J. C., Home, P., Eddy, B., Gregusta, R., and Fraser, C. M., 1984 Alphas-adrenergic receptor structure, Mol. Pharmacol. 26:196–205.PubMedGoogle Scholar
  233. Vergara, J., Tsien, R. Y., and Delay, M., 1985, Inositol 1,4,5-trisphosphate: A possible chemical link in excitation—contraction coupling in muscle, Proc. Natl. Acad. Sci. U.S.A. 82:6352–6356.PubMedGoogle Scholar
  234. Verghese, M. W., Smith, C. D., and Snyderman, R., 1985, Potential role for a guanine nucleotide regulatory protein in chemoattractant receptor mediated polyphosphoinositide metabolism, Cat± mobilization and cellular respiration by leukocytes, Biochem. Biophys. Res. Commun. 127:450–457.PubMedGoogle Scholar
  235. Vickers, J. D., Kinlough-Rathbone, R. L., and Mustard, J. F., 1984, Changes in the platelet phosphoinositides during the first minute after stimulation of washed rabbit platelets with thrombin, Biochem. J. 219:25–31.PubMedGoogle Scholar
  236. Vincentini, L. M., Ambrosini, A., DiVirgilio, F., Pozzan, T., and Meldolesi, J., 1985, Muscarinic receptor-induced phosphoinositide hydrolysis at resting cytosolic Cat+ concentration in PC12 cells, J. Cell. Biol. 100:1330–1333.Google Scholar
  237. Volpe, J., Salviati, G., DiVirgilio, R., and Pozzan, T., 1985, Inositol 1,4,5-trisphosphate induces calcium release from sarcoplasmic reticulum of skeletal muscle, Nature 316:347–349.PubMedGoogle Scholar
  238. Volpi, M., Yassin, R., Naccache, P. H., and Sha’afi, R. I., 1983, Chemotactic factors cause rapid decreases in phosphatidylinositol, 4,5-bisphosphate and phosphatidylinositol 4-monophosphate in rabbit neutrophils, Biochem. Biophys. Res. Commun. 112:957–964.PubMedGoogle Scholar
  239. Volpi, M., Naccache, P. H., Molski, T. F. P., Shefcyk, J., Huang, C.-K., Marsh, M. L., Munoz, J., Becker, E. L., and Sha’afi, R. I., 1985, Pertussis toxin inhibits fMet-Leu-Phe but not phorbol ester stimulated changes in rabbit neutrophils, Proc. Natl. Acad. Sci. U.S.A. 82:2708–2712.PubMedGoogle Scholar
  240. Wallace, M. A., and Fain, J. N., 1985, Guanosine 5’-O-thiotriphosphate stimulates phospholipase C activity in plasma membranes of rat hepatocytes, J. Biol. Chem. 260:9527–9530.PubMedGoogle Scholar
  241. Wallace, M. A., Randazzo, P., Li, S. Y., and Fain, J. N., 1982, Direct stimulation of phosphatidylinositol degradation by addition of vasopressin to purified rat liver plasma membranes, Endocrinology 111:341–343.PubMedGoogle Scholar
  242. Wallace, M. A., Poggioli, J., Giraud, F., and Claret, M., 1983, Norepinephrine-induced loss of phosphatidylinositol from isolated rat liver plasma membrane, FEBS Len. 156:239–243.Google Scholar
  243. Watkins, P. A., Moss, J., Bums, D. L., Hewlett, E. L., and Vaughan, M., 1984, Inhibition of bovine outer rod segment GTPase by Bordetella pertussis toxin, J. Biol. Chem. 259:1378–1381PubMedGoogle Scholar
  244. Weiss, S. J., McKinney, J. S., and Putney, J. W., Jr., 1982, Receptor-mediated net breakdown of phosphatidylinositol 4,5-bisphosphate in parotid acinar cells, Biochem. J. 206:555–560.PubMedGoogle Scholar
  245. Wilson, D. B., Bross, T. E., Hofmann, S. L., and Majerus, P. W., 1984, Hydrolysis of polyphosphoinositides by purified sheep seminal vesicle phospholipase C enzymes, J. Biol. Chem. 259:11718–11724.PubMedGoogle Scholar
  246. Wilson, D. B., Connolly, T. M., Bross, T. E., Majerus, P. W., Sherman, W. R., Tyler, A. N., Rubin, L. J., and Brown, J. E., 1985, Isolation and characterization of the inositol cyclic phosphate products of polyphosphoinositide cleavage by phospholipase C, J. Biol. Chern. 260:13496–13501.Google Scholar
  247. Wirthensohn, G., Lefrank, S., and Guder, W. G., 1984, Phospholipid metabolism in rat kidney cortical tubules. II. Effects of hormones on 32p incorporation, Biochem. Biophys. Acta 795:401–410.PubMedGoogle Scholar
  248. Wolf, B. A., Comens, P. G., Ackermann, K. E., Sherman, W. R., and McDaniel, M. L., 1985, The digitonin-permeabilized pancreatic islet model, Biochem. J. 227:965–969PubMedGoogle Scholar
  249. Yano, K., Nakashima, S., and Nozawa, Y., 1983, Coupling of polyphosphoinositide break-down with calcium efflux in formyl-methionyl-leucyl-phenylalanine-stimulated rabbit neutrophils, FEBS Lett. 161:296–300.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • John H. Exton
    • 1
  1. 1.Howard Hughes Medical Institute and Department of Molecular Physiology and BiophysicsVanderbilt University School of MedicineNashvilleUSA

Personalised recommendations