Abstract
Four amphipathic molecules with known local anesthetic activity, dibucaine, tetracaine, chlorpomazine, and quinacrine, inhibited the binding ofl-[3H]glutamic acid to rat brain synaptic plasma membranes and to the purified glutamate binding protein. Neither haloperidol nor diphenylhydantoin had significant inhibitory effects on the glutamate binding activity of the membranes or of the purified protein. The amphipathic drugs apparently inhibitedl-[3H]glutamate binding to synaptic membranes by a mixed type of inhibition. The inhibitory activity of quinacrine on glutamate binding to the synaptic membranes was greater in a low ionic strength, Ca2+-free buffer medium, than in a physiologic medium (Krebs-Henseleit buffer). Removal of Ca2+ from the Krebs solution enhanced quinacrine's inhibition of glutamate binding. Quinacrine up to 1 mM concentration did not inhibit the high affinity Na+-dependentl-glutamate transport in these membrane preparations. The importance of Ca2+ in the expression of quinacrine's effects on the glutamate binding activity of synaptic membranes and the observed tetracaine and chlorpromazine-induced increases in the transition temperature for the glutamate binding process of these membranes, were indicative of an interaction of the local anesthetics with the lipid environment of the glutamate binding sites.
Similar content being viewed by others
References
Seeman, P. 1972. The membrane action of anesthetics and tranquilizers. Pharmacol. Rev. 24:583–655.
Seeman, P. 1966. Membrane stabilization by drugs: tranquilizers, steroids, and anesthetics. Int. Rev. Neurobiol. 9:145–221.
Wang, H. H., Earnest, J., andChan, D. 1980. Interaction of local anesthetics with biological and model membranes. Pages 483–487,in Fink, B. R. (ed.), Molecular Mechanisms of Anesthesia, Raven Press, New York.
Narahashi, T., Frazier, D. T., andYamada, M. 1970. The site of action and active form of local anesthetics. I. Theory and pH experiments with tertiary compounds. J. Pharmacol. Exp. Ther. 171:32–44.
Narahashi, T., Frazier, D. T., andMoore, J. W. 1972. Comparison of tertiary and quaternary amine local anesthetics in their ability to depress membrane ionic conductances. J. Neurobiol. 3:267–276.
Skou, J. C. 1954. Local anesthetics. I. The blocking potencies of some local anesthetics and of butyl alcohol determined on peripheral nerves. Acta Pharmacol. Toxicol. 10:281–291.
Schwartz, W., Palade, P. T., andHille, B. 1977. Local anesthetics: Effect of pH on use-dependent block of sodium channels on frog muscles. Biophys. J. 20:343–368.
Grühagen, H-H., andChangeux, J-P. 1976. Studies on the electrogenic action of acetylcholine with torpedo marmorata electric organ. J. Mol. Biol. 106:497–516.
Adams, P. R., andFeltz, A. 1977. Interaction of a fluorescent probe with acetylcholine-activated synaptic membrane. Nature 269:609–611.
Adams, P. R., andBanks, F. W. 1980. Actions of anesthetics and anticonvulsants on synaptic channels. Pages 95–109,in Fink, B. R. (ed.), Molecular Mechanisms of Anesthesia, Raven Press, New York.
Flicker, C., andGeyer, M. A. 1982. Behavior during hippocompal microinfusions. III. Lidocaine versus picrotoxin. Brain Res. Rev. 4:129–136.
Herz, A., andZieglgansberger, W. 1968. The influence of microelectrophoretically applied biogenic amines, cholinomimetics and procaine on synaptic excitation in the corpus striatum. Int. J. Neuropharmacol. 7:221–230.
Stritchartz, G. R. 1976. Molecular mechanisms of nerve block by local anesthetics. Anesthesiology 45:421–441.
Feinstein, M. B. 1964. Reaction of local anesthetics with phospholipids. J. Gen. Physiol. 48:357–374.
Weber, M., andChangeux, J-P. 1974. Binding of naja nigricollis [3H] α-toxin to membrane fragments from electrophorus and torpedo electric organs. Mol. Pharmacol. 10:35–40.
Heidman, T., andChangeux, J-P. 1978. Structural and functional properties of the acetylcholine receptor protein in its purified and membrane-bound states. Annu. Rev. Biochem. 47:317–357.
Blanchard, S. G., Elliot, J., andRaftery, M. A. 1979. Interaction of local anesthetics with torpedo californica membrane-bound acetylcholine receptor. Biochemistry 18:5880–5885.
Evans, R. H., Francis, A. A., andWatkins, J. C. 1977. Differential antagonism by chlorpromazine and diazepam of frog motoneurone depolarization induced by glutamaterelated amino acids. Europ. J. Pharmacol. 44:325–330.
Foster, A. C., andRoberts, P. J. 1978. High affinityl-[3H]glutamate binding to postsynaptic receptor sites on rat cerebellar membranes. J. Neurochem. 31:1467–1477.
Michaelis, E. K., Michaelis, M. L., Chang, H. H., Grubbs, R. D., andKuonen, D. R. 1981. Molecular characteristics of glutamate receptors in the mammalian brain. Molec. Cell. Biochim. 38:163–179.
Baudry, M., andLynch, G. 1981. Characterization of two [3H]glutamate binding sites in rat hippocampal membranes. J. Neurochem. 36:811–820.
Foster, A. C., Mena, E. E., Fagg, G. E., andCotman, C. W. 1981. Glutamate and aspartate binding sites are enriched in synaptic junctions isolated from rat brain. J. Neuroscience 1:620–625.
Honoré, T., Lowridsen, J., andKrogsgaard-Larsen, P. 1981. Ibotenic acid analogues as inhibitors of [3H]glutamic acid binding to cerebellar membranes. J. Neurochem. 36:1302–1304.
Bizierre, K., Thompson, H., andCoyle, J. T. 1980. Characterization of specific highaffinity binding sites forl-[3H]glutamic acid in rat brain membranes. Brain Res. 183:421–423.
Chang, H. H., andMichaelis, E. K. 1980. Effects ofl-glutamic acid on synaptosomal and synaptic membrane Na+ fluxes and (Na+−K+)-ATPase. J. Biol. Chem. 255:2411–2417.
Kanner, B. I. 1978. Active transport of γ-aminobutyric acid by membrane vesicles isolated from rat brain. Biochemistry 17:1207–1211.
Shariff, N. A., andRoberts, P. J. 1980. Problems associated with the binding ofl-glutamic acid to synaptic membranes: Methodological aspects. J. Neurochem. 34:779–784.
Michaelis, E. K., Michaelis, M. L., andGrubbs, R. D. 1980. Distinguishing characteristics between glutamate and kainic acid binding sites in brain synaptic membranes. FEBS Lett. 118:55–57.
Michaelis, E. K. 1975. Partial purification and characterization of a glutamate-binding glycoprotein from rat brain. Biochem. Biophys. Res. Communic. 65:1004–1012.
Michaelis, E. K., Michaelis, M. L., Stormann, T. M., Chittenden, W. L., andGrubbs, R. D. 1983. Purification and molecular characterization of the brain synaptic membrane glutamate-binding protein. J. Neurochem. 40:1742–1753.
Michaelis, E. K. 1979. The glutamate receptor-like protein of brain synaptic membranes is a metalloprotein. Biochem. Biophys. Res. Communic. 87:106–113.
Kanner, B. I., andSharon, I. 1978. Active transport ofl-glutamate by membrane vesicles isolated from rat brain. Biochemistry 17:3949–3953.
Michaelis, E. K., Belieu, R. M., Grubbs, R. D., Michaelis, M. L., andChang, H. H. 1982. Differential effects of metal ligands on synaptic membrane glutamate binding and uptake systems. Neurochem. Res. 7:417–430.
Lowry, O. H., Rosebrough, N. J., Farr, A. L., andRandall, R. J. 1951. Protein measurement with the folin phenol reagent. J. Biol. Chem. 193:265–275.
Cools, A. R., andVan Rossum, J. M. 1976. Excitation-mediating and inhibition-mediating dopamine-receptors. Psychopharmacol. (Berl.) 45:243–254.
Woodbury, D. M. 1955. Effect of diphenylhydantoin on electrolytes and radiosodium turnover in brain and other tissues of normal, hyponatremic and postictal rats. J. Pharmacol. Exp. Therap. 115:74–95.
Ohnishi, S., andIto, T. 1974. Calcium-induced phase separations in phosphatidylserine-phosphatidylcholine membranes. Biochemistry 13:881–887.
Cullis, P. R., Hornby, A. P., andHope, M. J. 1980. Effects of anesthetics on lipid polymorphism. Pages 397–403,in Fink, B. R. (ed.), Molecular Mechanisms of Anesthesia, Raven Press, New York.
Papahadjopoulos, D. 1970. Phospholipid model membranes. III. Antagonistic effects of Ca2+ and local anesthetics on the permeability of phosphatidylserine vesicles. Biochim. Biophys. Acta 211:467–477.
Seeman, P., Kwant, W. O., Goldberg, M., andChau-Wong, M. 1971. The effects of ethanol and chlopromazine on the passive membrane permeability to Na+. Biochim. Biophys. Acta 241:349–355.
Dipple, I., Gordon, L. M., andHouslay, M. D. 1982. The activity of 5′-nucleotidase in liver plasma membranes is affected by the increase in bilayer fluidity achieved by anionic drugs but not by cationic drugs. J. Biol. Chem. 257:1811–1815.
Michaelis, E. K., Zimbrick, J. D., McFaul, J. A., Lampe, R. A., andMichaelis, M. L. 1980. Ethanol effects on synaptic glutamate receptors and on liposomal membrane structure. Pharmacol. Biochem. Behav. 13, Suppl. 1, 197–202.
Low, P. S., Lloyd, D. H., Stein, T. M. andRogers, J. A. 1979. Calcium displacement by local anesthetics. J. Biol. Chem. 254:1419–1425.
Volpi, M., Sha'afi, R. I., Epstein, P. M., Andre-Nyak, D. M., andFeinstein, M. B. 1981. Local anesthetics, nepacrine, and propranolol are antagonists of calmodulin. Proc. Natl. Acad. Sci. (USA) 78:795–799.
Mueller, D. M., andLee, C. P. 1982. Inhibition of the energy-linked fluorescence response of quinacrine with local anesthetics. FEBS Lett. 137:45–48.
Leterrier, F., Rieger, F., andMariaud, J. F. 1973. Comparative study of the action of phenothiazine and para-fluorobutyrophenone derivatives on rat brain membranes using the spin label technique. J. Pharmacol. Exper. Therap. 186:609–615.
Takishima, K., Shimizu, H., Setaka, M., andKwan, T. 1980. A spin-label study of the effects of drugs on calcium release from isolated sacroplasmic reticulum vesicles. J. Biochem. 87:305–312.
Chang, H. H., andMichaelis, E. K. 1982.l-Glutamate effects on electrical potentials of synaptic plasma membrane vesicles. Biochim. Biophys. Acta 688:285–294.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Michaelis, E.K., Magruder, C.D., Lampe, R.A. et al. Effects of amphipathic drugs onl-[3H]glutamate binding to synaptic membranes and the purified binding protein. Neurochem Res 9, 29–44 (1984). https://doi.org/10.1007/BF00967657
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00967657