Ethanol and Phospholipid Dependent Signal Transduction: The View from the Liver

  • Jan B. Hoek
  • Tomoyuki Nomura
  • Katsuyoshi Higashi

Abstract

Receptor-mediated signal transduction processes are common targets of acute or chronic ethanol treatment, both in brain and in peripheral tissues (reviewed in Hoffman and Tabakoff, 1990; Hoek et al, 1992). G protein-linked receptors coupled to adenylate cyclase were studied by several groups in different brain membrane preparations (Hoffman and Tabakoff, 1990). These studies identified the receptor-activated Gs protein α subunit as a likely target of acute ethanol actions in the central nervous system. The sensitivity to ethanol varied both with the receptor and the membrane preparation. Chronic ethanol treatment in vivo decreased the sensitivity to ethanol of adenylate cyclase activation (Hoffman and Tabakoff, 1990). Adenylate cyclase has also been recognized as an indirect target for ethanol in the studies of Diamond and coworkers (1991). Ethanol-induced changes in cellular adenosine uptake affected the extracellular level of this agonist; intracellular responses were determined by the type of adenosine receptors available on specific cells. Long-term ethanol treatment in vitro was associated with a decrease in the expression of the αs subunit for activation of adenylate cyclase (Mochly-Rosen et al, 1988).

Keywords

Hydrolysis Adenosine Serotonin Glucagon Neuroblastoma 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Burgess, G.M., Bird, G.St.J., Obie, J.F., and Putney, J.W. (1991) The mechanism for synergism between phospholipase C- and adenylate cyclase-linked hormones in liver. J.Biol.Chem. 266: 4772–4781.PubMedGoogle Scholar
  2. Danoff, S.K., Ferris, C.D., Donath, C., Fischer, G.A., Munemitsu, S., Ullrich, A., Snyder, S.H., and Ross, C.A. (1991) Inositol 1,4,5-trisphosphate receptors: Distinct neuronal and nonneuronal forms derived by alternative splicing differ in phosphorylation. Proc. Natl. Acad. Sci., U.S.A. 88: 2951–2955.PubMedCrossRefGoogle Scholar
  3. Diamond, I., Nagy, L., Mochly-Rosen, D. and Gordon, A. (1991) The role of adenosine and adenosine transport in ethanol-induced cellular tolerance and dependence. Possible biologic and genetic markers of alcoholism. Ann. N.Y. Acad. Sci., 625: 473–487.PubMedCrossRefGoogle Scholar
  4. Deitrich, R.A., Dunwiddie, T.V., Harris, R.A. and Erwin, V.G. (1989) Mechanism of action of ethanol: Initial central nervous system actions. Pharmacol. Rev. 41: 489–537.PubMedGoogle Scholar
  5. Gonzales, R.A., Thiess, C. and Crews, F.T. (1986) Effectys of ethanol on stimulated inositol phosphate hydrolysis in rat brain. J. Pharmacol. Exp. Therap. 237: 92–98.Google Scholar
  6. Higashi, K. and Hoek, J.B. (1991) Ethanol causes desensitization of receptor-mediated phospholipase C activation in isolated hepatocytes. J. Biol. Chem. 266: 2178–2190.PubMedGoogle Scholar
  7. Hoek, J.B., Thomas, A.P., Rubin, R. and Rubin, E. (1987) Ethanol-induced mobilization of calcium by activation of phosphoinositide-specific phospholipase C in intact hepatocytes. J. Biol. Chem. 262: 682–691.PubMedGoogle Scholar
  8. Hoek, J.B., Thomas, A.P. and Rubin, R. (1988) Ethanol-induced activation of phospholipase C activation is inhibited by phorbol esters in intact hepatocytes. Biochem. J. 251: 865–871.PubMedGoogle Scholar
  9. Hoek, J.B., Taraschi, T.F., Higashi, K., Rubin, E. and Thomas, A.P. (1990) Phospholipase C activation by ethanol in rat hepatocytes is unaffected by chronic ethanol feeding. Biochem. J. 272: 59–64.PubMedGoogle Scholar
  10. Hoek, J.B., Thomas, A.P., Rooney, T.A., Higashi, K. and Rubin, E. (1992) Ethanol and signal transduction in the liver. FASEB J. 6: 2386–2396.PubMedGoogle Scholar
  11. Hoffman, P.L. and Tabakov, B. (1990) Ethanol and guanine nucleotide binding proteins: a selective interaction. FASEB J. 4, 2612–2622.PubMedGoogle Scholar
  12. Hoffman, P.L., Moses, F., Luthin, G.R. and Tabakoff, B. (1986) Acute and chronic effects of ethanol on receptor-mediated phosphatidylinositol 4, 5-bisphosphate breakdown in mouse brain. Mol. Pharmacol. 30: 13–18.PubMedGoogle Scholar
  13. Messing, R.O., Sneade, A.B. and Savidge, B. (1990) Protein kinase C participates in up-regulation of dihydropyridine-sensitive calcium channels by ethanol. J.Neurochem. 55: 1383–1389.PubMedCrossRefGoogle Scholar
  14. Mochly-Rosen, D., Chang, F.-U., Cheever, L., Kim, M., Diamond, I. and Gordon, A.S: (1988) Chronic ethanol causes heterologous desensitization by reducing αs mRNA. Nature 333: 848–850.PubMedCrossRefGoogle Scholar
  15. Nagy, L.E. (1992) Ethanol metabolism and inhibition of nucleoside uptake lead to increased extracellular adenosine in hepatocytes. Am. J. Physiol. 262: C1175 - C1180.PubMedGoogle Scholar
  16. Rooney, T.A., Hager, R., Rubin, E. and Thomas, A.P. (1989) Short-chain alcohols activate guanine nucleotide-dependent phosphoinositidase C in turkey erythrocyte membranes. J. Biol. Chem. 264: 6817–6822.PubMedGoogle Scholar
  17. Rubin, R. and Hoek, J.B. (1990), Inhibition of ethanol-induced platelet activation by agents that elevate cAMP. Thrombosis Res. 58: 625–632.CrossRefGoogle Scholar
  18. Shearman, M.S., Sekiguchi, K. and Nishizuka, Y. (1989) Modulation of ion channel activity: A key function of the protein kinase C enzyme family. Pharmacol. Rev. 41, 211–237.PubMedGoogle Scholar
  19. Simonsson, P., Sun, G.Y., Vecsei, L. and Alling, C. (1989H) Ethanol effects on bradykinin-stimulated phosphoinositide hydrolysis in NG108-15 neuroblastoma-glioma cells. Alcohol 6: 475–479.PubMedCrossRefGoogle Scholar
  20. Simonsson, P., Hansson, E. and Alling, C. (1989b) Ethanol potentiates serotonin-stimulated inositol lipid metabolism in primary astroglial cell cultures. Biochem. Pharmacol. 38, 2801–2805.PubMedCrossRefGoogle Scholar
  21. Simonsson, P., Rodriguez, F.D., Loman, N. and Alling, C. (1991) G-proteins coupled to phospholipase C: molecular targets of long-term ethanol exposure.Google Scholar
  22. Smith, T.L., Yamamura, H.I. and Lee, L. (1986) Effect of ethanol on receptor-stimulated phosphatidic acid and polyphosphoinositide metabolism in mouse brain. Life Sci. 39: 1675–1684.PubMedCrossRefGoogle Scholar
  23. Smith, T.L. (1990) The effects of acute exposure to ethanol on neurotensin and guanine nucleotide stimulation of phospholipase C activity in intact NIE-115 neuroblastoma cells. Life Sci. 47:PL115–PL119.PubMedCrossRefGoogle Scholar
  24. Thomas, A.P., Renard, D.C. and Rooney, T.A. (1991) Spatial and temporal organization of calcium signalling in hepatocytes. Cell Calcium, 12: 111–126.PubMedCrossRefGoogle Scholar
  25. Woods, N.M., Cuthbertson, K.S.R. and Cobbold, P.H. (1986) Repetitive transient rises in cytoplasmic free calcium in hormone-stimulated hepatocytes. Nature 319: 600–602.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Jan B. Hoek
    • 1
  • Tomoyuki Nomura
    • 1
  • Katsuyoshi Higashi
    • 1
  1. 1.Department of Pathology and Cell BiologyThomas Jefferson UniversityPhiladelphiaUSA

Personalised recommendations