Abstract
The underlying molecular events by which EtOH induces its profound deleterious effects on the developing central nervous system (CNS) are still poorly understood. In the past, the accepted scientific view of the effect of EtOH was that it altered neuronal activity by virtue of a non specific interaction with neuronal membranes. However, recent developments suggest that its action may be directed toward pre- and/or post-synaptic events, including synthesis, turnover, release, binding of neurotransmitters to receptor sites, and second messenger systems. In the present chapter, we present data showing a selective interaction of EtOH with muscarinic receptor-stimulated phosphoinositide hydrolysis during postnatal development in the rat suggesting, therefore, that this system may represent a specific and relevant target for the developmental neurotoxicity of EtOH.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Alling, C, Gustavsson, L., Mansson, J.E., Benthin, G., and Auggard, E., 1984, Phosphatidyl-ethanol formation in rat organs after ethanol treatment, Biochem Biophys Acta 793: 119–122.
Asaoka, Y., Kikkawa, U., Sekiguchi, K, Shearman, M.S., Kosaka, Y, Nakano, Y., Satoh, T. and Nishizuka, Y., 1988, Activation of brain-specific protein kinase C subspecies in the presence of phosphatidylethanol, FEBS Lett 231: 221–224.
Ashkenazi, A., Dramachandran, J., and Capon, D.J., 1989, Acetylcholine analogue stimulates DNA synthesis in brain derived cells via specific muscarinic receptor subtypes, Nature 340: 146–150.
Balduini, W., Murphy, S.D., and Costa, L.G., 1987, Developmental changes in muscarinic receptor-stimulated phosphoinosiitde metabolism in rat brain, J Pharmacol Exp Ther 241: 421–427.
Balduini, W., and Costa, L.G., 1989, Effects of ethanol on muscarinic receptor-stimulated phosphoinositide metabolism during brain development, J Pharmacol Exp Ther 250: 541–547.
Balduini, W, and Costa, L.G., 1990, Developmental neurotoxicity of ethanol: in vitro inhibition of muscarinic receptor-stimulated phosphoinositide metabolism in brain from neonatal but not adult rats, Brain Res 512: 248–252.
Balduini, W., Murphy, S.D., and Costa, L.G., 1990, Characterization of cholinergic muscarinic receptor-stimulated phosphoinositide metabolism in brain from immature rats, J Pharmacol Exp Ther 253: 573–579.
Balduini, W., Candura, S.M., and Costa, L.G., 1991a, Regional development of carbachol-, glutamate-, norepinephrine-, and serotonin-stimulated phosphoinositide metabolism in rat brain, Dev Brain Res 62: 115–120.
Balduini, W., Candura, S.M., Manzo, L., Cattabeni, F., and Costa, L.G., 1991b, Time-, concentration-, and age- dependent inhibition of muscarinic receptor-stimulated phosphoinositide metabolism by ethanol in the developing rat brain, Neurochem Res 16: 1235–1240.
Brans, E.M., Krackeberg, T.W., Stibler, H., Cerven, E., and Borg, S., 1984, The effects of ethanol exposure during the brain growth spurt in rats, Teratology 29: 251–258.
Candura, S.M., Balduini, W., and Costa, L.G., 1991, Interaction of short chain aliphatic alcohols with muscarinic receptor-stimulated phosphoinositide metabolism in cerebral cortex from neonatal and adult rats, NeuroToxicology 12: 23–32.
Candura, S.M., Manzo, L., and Costa, L.G., 1992, Inhibition of muscarinic receptor and G-protein-dependent phosphoinositide metabolism in cerebrocortical membranes from neonatal rats by ethanol, Neurotoxicology 13: 281–288.
Dobbing, J., and Sands, J., 1979, Comparative aspects of the brain growth spurt, Early Human Develop 3: 79–83.
Gottlieb, A., Keydar, I., and Epstein, H.T., 1977, Rodent brain growth stages: an analytical review, Biol Neonate 32: 166–176.
Grant, K.A., and Samson, H.H., 1982, Ethanol and tertiary butanol-induced microencephaly in the neonatal rat: comparison of brain growth parameters, Neurobehav Toxicol Teratol 4: 315–321
Grant, K.A., and Samson, H.H., 1984, n-Propanol-induced microencephaly in the neonatal rat, Neurobehav Toxicol Teratol 6: 165–169.
Heacock, A.M., Fisher, S.K., and Agranoff, B.W., 1987, Enhanced coupling of neonatal muscarinic receptors in rat brain to phosphoinositide turnover, J Neurochem 48: 1904–1911.
Hoek, J.B., and Rubin, E., 1990, Alcohol and membrane-associated signal tranduction, Alcohol & Alcoholism 25: 143–156.
Hohman, C.F., Brooks, A.R., and Coyle, J.T., 1988, Neonatal lesions of the basal forebrain cholinergic neurons results in abnormal cortical development, Dev Brain Res 42: 253–264.
Hunt, W.A., and Dalton, T.K., 1976, Regional brain acetylcholine levels in rats acutely treated with ethanol or rendered ethanol-dependent, Brain Res 109: 628–631.
Moon, K.H., Lee, S.Y., and Rhee, S.G., 1989, Developmental changes in the activities of phospholipase C, 3-kinase and 5-phosphatase in rat brain, Biochem Biophys Res Comm 164: 370–374.
Nordberg, A., and Wahlstrom, G., 1982, Tolerance, physical dependence and changes in muscarinic receptor binding sites after chronic ethanol treatment in the rat, Life Sci 31: 277–287.
Samson, H.H., and Diaz, J., 1982, Effects of neonatal ethanol exposure on brain development in rodents. in: “Fetal Alcohol Syndrome. Vol III. Animal Studies”. Abel E.L. ed., Boca Raton, CRC Press, pp 131–150.
Smith, T.L., 1983, Influence of chronic ethanol consumption on muscarinic cholinergic receptors and their linkage to phospholipid metabolism in mouse synaptosomes Neuropharmacology 22: 661–663.
Sonderegger, T.L., Colbern, D., Calmes, H., Corbitt, S., and Zimmerman, E., 1982, Methodological note: intragastric intubation of ethanol to rat pups, Neurobehav Toxicol Teratol 4: 477–481.
Sposi, N.M., Bottero, L., Cossu, G., Russo, G., Testa, U., and Peschile, C., 1989, Expression of protein kinase C genes during ontogenic development of the central nervous system, Mol Cell Biol 9: 2284–2288.
Streissguth, A.P., Landesman-Dwyer, S., Martin, J.C., and Smith D.W., 1980, Teratogenic effects of alcohol in humans and laboratory animals, Science 209: 353–361.
Tabakoff, B., Munoz-Marcus, M., and Fields, J. Z., 1979, Chronic ethanol feeding produces an increase in muscarinic cholinergic receptors in mouse brain, Life Sei 25: 2173–2180.
Van Hoof, C.O.M., De Graan, P.N.E., Oestriecher, A.B., and Gispen, W.H., 1989, Muscarinic receptor activation stimulates B50/GAP43 phosphorylation in isolated nerve growth cones, J Neurosci 9: 3753–3759.
West, J.R., and Pierce, D.R., 1986, Perinatal alcohol exposure and neuronal damage, in: Alcohol and Brain Development, J.R. West, ed., Oxford University Press, New York, pp. 120–157.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1993 Springer Science+Business Media New York
About this chapter
Cite this chapter
Balduini, W., Cattabeni, F., Renò, F., Costa, L.G. (1993). The Muscarinic Receptor-Stimulated Phosphoinositide Metabolism as a Potential Target for the Neurotoxicity of Ethanol During Brain Development. In: Alling, C., Diamond, I., Leslie, S.W., Sun, G.Y., Wood, W.G. (eds) Alcohol, Cell Membranes, and Signal Transduction in Brain. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2470-0_23
Download citation
DOI: https://doi.org/10.1007/978-1-4615-2470-0_23
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-6052-0
Online ISBN: 978-1-4615-2470-0
eBook Packages: Springer Book Archive