Skip to main content
SpringerLink
Log in

Inositol Trisphosphate and Diacylglycerol as Intracellular Second Messengers

  • Chapter
Mechanisms of Receptor Regulation

Part of the book series: New Horizons in Therapeutics ((NHTH))

Abstract

Inositol lipids play a central role in the signal transduction mechanism used by a large number of hormones and neurotransmitters. The primary action of these agonists is to stimulate the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to produce diacylglycerol (DG), which remains in the plane of the membrane, and inositol 1,4,5-trisphosphate (IP3), which is released to the cytoplasm (for details see Michell, Chapter 6). The fascinating aspect of this receptor mechanism is that both products resulting from the agonist-dependent cleavage of PIP2 appear to function as second messengers to activate separate cellular processes. The neutral DG activates a protein kinase (C-kinase) that phosphorylates specific proteins (Takai et al., 1979; Kishimoto et al., 1980; Kuo et al., 1980; Nishizuka, 1983), whereas IP3 appears to function as a second messenger to mobilize intracellular calcium (Berridge, 1983; Streb et al., 1983; Berridge et al., 1984b; Burgess et al., 1984; Joseph et al., 1984).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • 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.

    PubMed  CAS  Google Scholar 

  • Abdel-Latif, A. A., Green, K., and Smith, J. P., 1979, Sympathetic denervation and the trisphosphoinositide effect in the iris smooth muscle: A biochemical method for the determination of alpha-adrenergic receptor denervation supersensitivity, J. Neurochem. 32: 225–228.

    Article  PubMed  CAS  Google Scholar 

  • Agranoff, B. W., Murthy, P., and Seguin, E. B., 1983, Thrombin-induced phosphodiesteratic cleavage of phosphatidylinositol bisphosphate in human platelets. J. Biol. Chem. 258: 2076–2078.

    PubMed  CAS  Google Scholar 

  • Akhtar, R. A., and Abdel-Latif, A. A., 1980, Requirement for calcium ions in acetylcholine- stimulated phosphodiesteratic cleavage of phosphatidyl-myo-inositol 4,5-bisphosphate in rabbit iris smooth muscle, Biochem. J. 192: 783–791.

    PubMed  CAS  Google Scholar 

  • Allison, J. H., 1978, Lithium and brain myo-inositol metabolism, in: Cyclitols and Phosphoinositides ( W. W. Wells, and F. Eisenberg, eds.), Academic Press, New York, pp. 507–519.

    Google Scholar 

  • Allison, J. H., and Stewart, M. A., 1971, Reduced brain inositol in lithium-treated rats, Nature (New Biol.) 233: 267–268.

    Article  CAS  Google Scholar 

  • Allison J. H., Blisner, M. E., Holland, W. H., Hipps, P. P., and Sherman W. R., 1976, Increased brain myo-inositol 1-phosphate in lithium-treated rats, Biochem. Biophys. Res. Commun. 71: 664–670.

    Article  PubMed  CAS  Google Scholar 

  • Aprison, M. H., Takahashi, R., andTachiki, K., 1978, Hypersensitive serotonergic receptors involved in clinical depression-a theory, in: Neuropharmacology and Behaviour ( B. Haber and M. H. Aprison, eds.), Plenum Press, New York, pp. 23–53.

    Google Scholar 

  • Aub, D. L., and Putney, J. W., 1984, Metabolism of inositol phosphates in parotid cells: Implications for the pathways of the phosphoinositide effect and for the possible messenger role of inositol trisphosphate, Life Sci. 34: 1347–1355.

    Article  PubMed  CAS  Google Scholar 

  • Bell, R. L., Kennerly, D. A., Stanford, N., and Majerus, P. W., 1979, Diglyceride lipase: A pathway for arachidonate release from human platelets, Proc. Natl. Acad. Sci. U.S.A. 76: 3238–3241.

    Article  PubMed  CAS  Google Scholar 

  • Bell, M. E., Peterson, R. G., and Eichberg, J., 1982, Metabolism of phospholipids in peripheral nerve from rats with chronic streptozotocin-induced diabetes: Increased turnover of phosphatidylinositol-4,5-bisphosphate, J. Neurochem. 39: 192–200.

    Article  PubMed  CAS  Google Scholar 

  • Berridge, M. J., 1983, Rapid accumulation of inositol trisphosphate reveals that agonists hydrolyse polyphosphoinositides instead of phosphatidylinositol,Biochem. J. 212:849–858.

    PubMed  CAS  Google Scholar 

  • Berridge, M. J., and Fain, J. N., 1979, Inhibition of phosphatidylinositol synthesis and the inactivation of calcium entry after prolonged exposure of the blowfly salivary gland to 5-hydroxytryptamine, Biochem. J. 178: 59–69.

    PubMed  CAS  Google Scholar 

  • Berridge, M. J., Downes, C. P., and Hanley, M. R., 1982, Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary gland, Biochem. J. 206: 587–595.

    PubMed  CAS  Google Scholar 

  • Berridge, M. J., 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.

    PubMed  CAS  Google Scholar 

  • Berridge, M. J., Buchan, P. B., and Heslop, J. P., 1984a, Relationship of polyphosphoinositide metabolism to the hormonal activation of the insect salivary gland to 5-hydroxytryptamine, Mol. Cell. Endocrinol. 36: 37–42.

    Article  PubMed  CAS  Google Scholar 

  • Berridge, M. J., Heslop, J. P., Irvine, R. F., and Brown, K. D., 1984b, Inositol trisphosphate formation and calcium mobilization in Swiss 3T3 cells in response to platelet-derived growth factor Biochem. J. 222: 195–206.

    PubMed  CAS  Google Scholar 

  • Billah, M. M., and Lapetina, E. G., 1982a, Rapid decrease of phosphatidyinositol 4,5-bis- phosphate in thrombin-stimulated platelets, J. Biol. Chem. 257: 12705–12708.

    PubMed  CAS  Google Scholar 

  • Billah, M. M., and Lapetina, E. G., 1982b, Evidence for multiple metabolic pools of phosphatidylinositol in stimulated platelets, J. Biol. Chem, 257: 11856–11859.

    PubMed  CAS  Google Scholar 

  • Brown, E., Kendall, D. A., and Nahorski, S. R., 1984, Inositol phospholipid hydrolysis in rat cerebral cortical slices: I. Receptor characterization, J. Neurochem. 42: 1379–1387.

    Article  PubMed  CAS  Google Scholar 

  • Bunney, W. E., Jr., Post, R. M., Andersen, A. E., and Kopanda, T., 1977, A neuronal receptor sensitivity mechanism in affective illness. Commun. Psycopharmacol. 1: 393–405.

    Google Scholar 

  • Burgess, G. M., Godfrey, P. P., McKinney, J. S., Berridge, M. J., Irvine, R. F., and Putney, J. W., 1984, The second messenger linking receptor activation to internal Ca release in liver, Nature, 309: 63–66.

    Article  PubMed  CAS  Google Scholar 

  • Castagna, M., Takai, Y., Kaibuchi, K., Sano, K., Kikkawa, U., and Nishizuka, Y., 1982, Direct activation of calcium-activated phospholipid-dependent protein kinase by tumour-promoting phorbol esters. J. Biol. Chem. 257: 7847–7851.

    PubMed  CAS  Google Scholar 

  • Creba, J. A., Downes, C. P., 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 Ca2 +-mobilizing hormones, Biochem. J. 212: 733–747.

    PubMed  CAS  Google Scholar 

  • Doolittle, R. F., Hunkapiller, M. W., Hood, L. E., Devare, S. G., Robbins, K. S., Aaronson, S. A., and Antoniades, H. N., 1983, Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor, Science 221: 275–277.

    Article  PubMed  CAS  Google Scholar 

  • Downes, C. P., 1983, Inositol phospholipids and neurotransmitter-receptor signalling mechanisms, Trends Neurosci. 6: 313–316.

    Article  CAS  Google Scholar 

  • Downes, C. P., Mussat, M. C., and Michell, R. H., 1982, The inositol trisphosphate phos- phomonoesterase of the human erythrocyte membrane, Biochem. J. 203: 169–177.

    PubMed  CAS  Google Scholar 

  • Downes, C. P., Dibner, M. D., and Hanley, M. R., 1983, Sympathetic denervation impairs agonist-stimulated phosphatidylinositol metabolism in rat parotid glands, Biochem. J. 214: 865–870.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Downward, J., Yarden, Y., Mayes, E., Scrace, G., Totty, N., Stockwell, P., Ullrich, A., Schlessinger, J., and Waterfield, M. D., 1984, Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences, Nature 307: 521–527.

    Article  PubMed  CAS  Google Scholar 

  • Durell, J., Sodd, M. A., and Friedel, R. O., 1968, Acetylcholine stimulation of the phosphodiesterase cleavage of guinea pig brain phosphoinositides, Life Sci. 7: 363–368.

    Article  PubMed  CAS  Google Scholar 

  • Fain, J. N., and Berridge, M. J., 1979, Relationship between phosphatidylinositol synthesis and recovery of 5-hydroxytryptamine-responsive Ca2+ flux in blowfly salivary gland, Biochem. J. 180: 655–661.

    PubMed  CAS  Google Scholar 

  • Garrison, J. C., Johnsen, D. E., and Campanile, C. P., 1984, Evidence for the role of phosphorylase kinase, protein kinase C, and other Ca2 +-sensitive protein kinases in the response of hepatocytes to angiotensin II and vasopressin, J. Biol. Chem. 259: 3283–3292.

    PubMed  CAS  Google Scholar 

  • Gillon, K. R. W., and Hawthorne, J. N., 1983, Transport of myo-inositol into endoneurial preparations of sciatic nerve from normal and streptozotocin-diabetic rats, Biochem. J. 210: 775–781.

    PubMed  CAS  Google Scholar 

  • Greene, D. A., De Jesus, P. V. Jr., and Winegrad, A. I., 1975, Effects of insulin and dietary myoinositol on impaired peripheral motor nerve conduction velocity in acute streptozotocin diabetes, J. Clin. Invest. 55: 1326–1336.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Hallcher, L. M., and Sherman, W. R., 1980, The effects of lithium ion and other agents on the activity of myo-inositol-l-phosphatase from bovine brain, J. Biol. Chem. 255: 10896–10901.

    PubMed  CAS  Google Scholar 

  • Hinton, B. T., White, R. W., and Setchell, B. P., 1980, Concentrations of myo-inositol in the luminal fluid of the mammalian testis and epididymis, J. Reprod. Fertil. 58: 395–399.

    Article  PubMed  CAS  Google Scholar 

  • Huerta-Bahena, J., and Garcia-Sainz, J. A., 1983, Inositol administration restores the sensitivity of liver cells formed during liver regeneration to alpha i-adrenergic amines, vasopressin and angiotensin II, Biochim. Biophys. Acta 763: 125–128.

    Article  PubMed  CAS  Google Scholar 

  • Igarashi, Y., and Kondo, Y., 1980, Acute effect of thryotropin on phosphatidylinositol degradation and transient accumulation of diacylglycerol in isolated thyroid follicles, Biochem. Biophys. Res. Commun. 97: 759–765.

    Article  PubMed  CAS  Google Scholar 

  • Jolles, J., Zwiers, H., van Dongen, C. J., Schotman, P., Wirtz, K. W. A., and Gispen, W. H., 1980, Modulation of brain polyphosphoinositide metabolism by ACTH-sensitive protein phosphorylation, Nature 286: 623–625.

    Article  PubMed  CAS  Google Scholar 

  • Jolles, J., Zwiers, H., Dekker, A., Wirtz, K. W. A., and Gispen, W. H., 1981, Corticotropin- (l–24)-tetracosapeptide affects protein phosphorylation and polyphosphoinositide metabolism in rat brain, Biochem. J. 194: 283–291.

    PubMed  CAS  Google Scholar 

  • Joseph, S. K., Thomas, A. P., Williams, R. J., Irvine, R. F., and Williamson, J. R., 1984, Myo-inositol 1,4,5-trisphosphate: A second messenger for the hormonal mobilization of intracellular Ca2+ in liver, J. Biol. Chem. 259: 3077–3081.

    PubMed  CAS  Google Scholar 

  • Kaibuchi, K., Sano, K., Hoshijima, M., Takai, Y., and Nishizuka, Y., 1982, Phosphatidylinositol turnover in platelet activation: Calcium mobilization and protein phosphorylation, Cell Calcium 3: 323–335.

    Article  PubMed  CAS  Google Scholar 

  • Kaibuchi, K., Takai, Y., Sawamura, M., Hoshijima, M., Fujikura, T., and Nishizuka, Y., 1983, Synergistic functions of protein phosphorylation and calcium mobilization in platelet activation, J. Biol. Chem. 258: 6701–6704.

    PubMed  CAS  Google Scholar 

  • Kaibuchi, K., Sawamura, M., Kalakami, Y., Kikkawa, U., Takai, Y., and Nishizuka, Y., Calcium and inositol phospholipid degradation in signal transduction, in: Inositol and Phosphoinositides (J. E. Bleasdale, J. Eichberg, and E. Hauser, ed.), Humana Press, Clifton, New Jersey (in press).

    Google Scholar 

  • Kishimoto, A., Takai, Y., Mori, T., Kikkawa, U., and Nishizuka, Y., 1980, Activation of calcium and phospholipid-dependent protein kinase by diacylglycerol, its possible relation to phosphatidylinositol turnover, J. Biol. Chem. 255: 2273–2276.

    PubMed  CAS  Google Scholar 

  • Knight, D. E., and Baker, P. F., 1983, The phorbol ester TPA increases the affinity of exocytosis for calcium in “leaky” adrenal medullary cells, FEBS Lett. 160: 98–100.

    Article  PubMed  CAS  Google Scholar 

  • Knight, D. E., and Scrutton, M. C., 1983, Direct evidence that cyclic nucleotides and 1,2- diacylglycerol modulate the Ca2+ sensitivity of secretion in platelets, J. Physiol. (Lond.) 49 P.

    Google Scholar 

  • Kraft, A. S., and Anderson, W. B., 1983, Phorbol esters increase the amount of Ca2+, phospholipid-dependent protein kinase associated with plasma membrane, Nature 301: 621–623.

    Article  PubMed  CAS  Google Scholar 

  • Kuo, J. F., Andersson, R. G. G., Wise, B. C., Mackerlova, L., Salomonsson, I., Brackett, N. L., Katoh, N., Shoji, M., and Wrenn, R. W., 1980, Calcium-dependent protein kinase: Widespread occurrence in various tissues and phyla of the animal kingdom and comparison of effects of phospholipids, calmodulin, and trifluoperazine. Proc. Natl. Acad. Sci. U.S.A. 77: 7039–7043.

    Article  PubMed  CAS  Google Scholar 

  • Litosch, I., Lee, H. S., and Fain, J. N., 1984, Phosphoinositide breakdwon in blowfly salivary gland, Am. J. Physiol. 246:cl41–cl47.

    Google Scholar 

  • Lyons, R. M., and Atherton, R. M., 1979, Characterization of a platelet protein phospho- rylated during the thrombin-induced release reaction, Biochemistry 18: 544–552.

    Article  PubMed  CAS  Google Scholar 

  • Malaisse, W. J., Lebrun, P., Herchuelz, A., Sener, A., and Malaisse-Lagae, F., 1983, Synergistic effect of a tumor-promoting phorbol ester and a hypoglycemic sulfonylurea upon insulin release, Endocrinology 113: 1870–1877.

    Article  PubMed  CAS  Google Scholar 

  • Martin, T. F. J., 1983, Thyrotropin-releasing hormone rapidly activates the phosphodiester hydrolysis of polyphosphoinositides in GH3 pituitary cells, J. Biol. Chem. 258: 14816–14822.

    PubMed  CAS  Google Scholar 

  • Margolis, R. U., Press, R., Altszuler, N., and Stewart, M. A., 1981, Inositol production by the brain in normal and alloxan-diabetic dogs, Brain Res. 28: 535–539.

    Article  Google Scholar 

  • Mastro, A. M., and Smith, M. C., 1983, Calcium-dependent activation of lymphocytes by ionophore, A23187 and a phorbol ester tumor promoter, J. Cell Physiol. 116: 51–56.

    Article  PubMed  CAS  Google Scholar 

  • Mayhew, J. A., Gillon, K. R. W., and Hawthorne, J. N., 1983, Free and lipid inositol, sorbitol and sugars in sciatic nerve obtained post-mortem from diabetic patients and control subjects, Diabetologia 24: 13–15.

    Article  PubMed  CAS  Google Scholar 

  • Michell, R. H., 1975, Inositol phospholipids and cell surface receptor function, Biochem. Biophys. Acta 415: 81–147.

    PubMed  CAS  Google Scholar 

  • Michell, R. H., Kirk, C. J., Jones, L. M., Downes, C. P., and Creba, J. A., 1981. The stimulation of inositol lipid metabolism that accompanies calcium mobilization in stimulated cells: Defined characteristics and unanswered questions, Phil. Trans. R. Soc. Lond. [Biol.] 296: 123–137.

    Article  CAS  Google Scholar 

  • Monaco, M. E., 1982, The phosphatidylinositol cycle in WRK-1 cells, J. Biol. Chem. 257: 2137–2139.

    PubMed  CAS  Google Scholar 

  • Naka, M., Nishikawa, M., Adelstein, R. S., and Hidaka, H., 1983, Phorbol ester-induced activation of human platelets is associated with protein kinase C phosphorylation of myosin light chains, Nature 306: 490–492.

    Article  PubMed  CAS  Google Scholar 

  • Natarajan, V., Dyck, P. J., and Schmid, H. H. O., 1981, Alterations of inositol lipid metabolism of rat sciatic nerve in streptozotocin-induced diabetes, J. Neurochem. 36: 413–419.

    Article  PubMed  CAS  Google Scholar 

  • Nishizuka, Y., 1983, Phospholipid degradation and signal translation for protein phosphorylation, Trends Biochem. Sci. 8: 13–16.

    Article  CAS  Google Scholar 

  • Palmano, K. P., Whiting, P. H., and Hawthorne, J. N., 1977, Free and lipid myo-inositol in tissues from rats with acute and less severe streptozotocin-induced diabetes, Biochem. J. 167: 229–235.

    PubMed  CAS  Google Scholar 

  • Prescott, S. M., and Majerus, P. W., 1983, Characterization of 1,2-diacylglycerol hydrolysis in human platelets, J. Biol. Chem. 258: 764–769.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Rebecchi, M. J., and Gerschengorn, M. C., 1983, Thyrotropin-releasing hormone stimulates rapid hydrolysis of phosphatidylinositol 4,5-bisphosphate by a phosphodiesterase in rat mammatropic pituitary cells: Evidence for an early calcium-independent action, Biochem. J. 216: 299–308.

    Google Scholar 

  • Rebecchi, M. J., Kolesnick, R. N., and Gershengorn, M. C., 1983, Thyrotropin-releasing hormone stimulates rapid loss of phosphatidylinositol and its conversion to 1,2-diacylglycerol and phosphatidic acid in rat mammotropic cells, J. Biol. Chem. 258: 227–234.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Rink, T. J., Smith S. W., and Tsien, R. Y., 1982, Cytoplasmic free Ca2+ in human platelets: Ca2 + thresholds and Ca-independent activation for shape-change and secretion, FEBS Lett. 148: 21–26.

    Article  PubMed  CAS  Google Scholar 

  • Rink, T. J., Sanchez, A., and Hallam, T. J., 1983, Diacylglycerol and phorbol ester stimulate secretion without raising cytoplasmic free calcium in human platelets, Nature 305: 317–319.

    Article  PubMed  CAS  Google Scholar 

  • Rittenhouse-Simmons, S., 1979, Production of diglyceride from phosphatidylinositol in activated human platelets. J. Clin. Invest. 63: 580–587.

    Article  PubMed  CAS  Google Scholar 

  • Rozengurt, E., 1983, Growth factors, cell proliferation and cancer: An overview, Mol. Biol. Med. 1: 169–181.

    PubMed  CAS  Google Scholar 

  • Sha’afi, R. I., White, J. R., Molski, T. F. P., Shefcyk, J., Volpi, M., Naccache, P. H., and Feinstein, M. B., 1983, Phorbol 12-myristate 13-acetate activates rabbit neutrophils without an apparent rise in the level of intracellular free calcium, Biochem. Biophys. Res. Commun. 114: 638–645.

    Article  PubMed  Google Scholar 

  • Sherman, W. R., Leavitt, A. L., Honchar, M. P., Hallcher, L. M., and Phillips, B. E., 1981, Evidence that lithium alters phosphoinositide metabolism: Chronic administration elevates primarily d-rayo-inositol-l-phosphate in cerebral cortex of the rat. J. Neurochem. 36: 1947–1951.

    Article  PubMed  CAS  Google Scholar 

  • Simmons, D. A., Winegrad, A. I., and Martin, D. B., 1982, Significance of tissue myo-inositol concentration in metabolic regulation in nerve, Science 217: 848–851.

    Article  PubMed  CAS  Google Scholar 

  • Streb, H., and Schulz, I., 1983, Regulation of cytosolic free Ca2+ concentration in acinar cells of rat pancreas, Am. J. Physiol. 245: G347–G357.

    PubMed  CAS  Google Scholar 

  • Streb, H., Irvine, R. F., Berridge, M. J., and Schulz, I., 1983, Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositiol 1,4,5-tris- phosphate, Nature 306: 67–69.

    Article  PubMed  CAS  Google Scholar 

  • Takai, Y., Kishimoto, A., Iwasa, Y., Kawahara, Y., Mori, T., and Nishizuka, Y., 1979, Calcium-dependent activation of a multifunctional protein kinase by membrane phospholipid, J. Biol. Chem. 254: 3692–3695.

    PubMed  CAS  Google Scholar 

  • Takenawa, T., Masaki, T., and Goto, K., 1983, Increase in norepinephrine-induced formation of phosphatidic acid in rat vas deferens after denervation, J. Biochem. 93:303–306.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Thomas, A. P., Alexander, J., and Williamson, J. R., 1984, Relationship between inositol polyphosphate production and the increase of cytosolic free Ca2+ induced by vasopressin in isolated hepatocytes, J. Biol. Chem. 259: 5574–5584.

    PubMed  CAS  Google Scholar 

  • Warfield, A. S., and Segal, S., 1978, Myo-inositol and phosphatidylinositol metabolism in synaptosomes from galactose-fed rats, Proc. Natl. Acad. Sci. U.S.A. 75: 4568–4572.

    Article  PubMed  CAS  Google Scholar 

  • Waterfield, M. D., Scrace, G. T., Whittle, N., Stroobant, P., Johnsson, A., Wasteson, Å., Westermark, B., Heldin, C.-H., Huang, J. S., and Deuel, T. F., 1983, Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus, Nature 304: 35–39.

    Article  PubMed  CAS  Google Scholar 

  • Whitfield, J. F., MacManus, J. P., and Gillan, D. J., 1973, Calcium-dependent stimulation by a phorbol ester (PMA) of thymic lymphoblast DNA synthesis and proliferation, J. Cell. Physiol. 82: 151–156.

    Article  PubMed  CAS  Google Scholar 

  • Whiting, P. H., Palmano, K. P., and Hawthorne, J. N., 1979, Enzymes of myo-inositol and inositol lipid metabolism in rats with streptozotocin-induced diabetes, Biochem. J. 179: 549–553.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. A.R.C. Unit of Insect Neurophysiology and Pharmacology, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, England

    Michael J. Berridge

Authors
  1. Michael J. Berridge
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Smith Kline and French Laboratories, Philadelphia, Pennsylvania, USA

    George Poste  & Stanley T. Crooke  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1985 Plenum Press, New York

About this chapter

Cite this chapter

Berridge, M.J. (1985). Inositol Trisphosphate and Diacylglycerol as Intracellular Second Messengers. In: Poste, G., Crooke, S.T. (eds) Mechanisms of Receptor Regulation. New Horizons in Therapeutics. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2131-6_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-2131-6_8

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-9259-3

  • Online ISBN: 978-1-4613-2131-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation