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Modulation of an acetylcholine receptor responsiveness by filipin and chlorpromazine studied in neurons ofAplysia californica

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Summary

  1. 1.

    The responsiveness ofAplysia acetylcholine receptors (AChR) was studied using a polyene antibiotic, filipin, which specifically complexes cholesterol, and another compound, chlorpromazine (CPZ), which inserts at the proteolipidic interface.

  2. 2.

    Both substances enhanced the evoked postsynaptic responses or responses to iontophoretic application of carbachol only on the H-type receptor (opening a Cl permeability), whereas at the same concentrations filipin was without effect on the D-type receptor (opening a cationic permeability) while CPZ depressed the D-type response.

  3. 3.

    The facilitation observed specifically for the H-type receptor was similar to that previously described after acetylcholinesterase (AChE) inhibition or when low concentrations of detergents were applied to this preparation. No additive effect was obtained after the addition of chlorpromazine following a maximal potentiation obtained with an anticholinesterase agent.

  4. 4.

    Since atAplysia central neurons, AChE is a membranal protein, we propose that the facilitation of H-type responses is attributable to the removal of a modulatory action of AChE on AChR. Filipin or chlorpromazine might disrupt the interaction between AChR and AChE.

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References

  • Anwyl, R., and Narahashi, T. (1980). Comparison of desensitization and time-dependent block of the acetylcholine receptor responses by chlorpromazine, cytochalasin B, triton X-100 and other agents.Br. J. Pharmacol. 6999–106.

    Google Scholar 

  • Ascher, P., Marty, A., and Neild, T. O. (1978). Lifetime and elementary conductance of the channels mediating the excitatory effects of acetylcholine inAplysia neurones.J. Physiol. (Lond.)278177–206.

    Google Scholar 

  • Borochov, H., and Shinitzky, M. (1976). Vertical displacement of membrane proteins mediated by changes in microviscosity.Proc. Natl. Acad. Sci. USA 734526–4530.

    Google Scholar 

  • Carp, J. S., Aronstam, A. S., Witkop, B., and Albuquerque, E. X. (1983). Electrophysiological and biochemical studies on enhancement of desensitization by phenothiazine neuroleptics.Proc. Natl. Acad. Sci. USA 80310–314.

    Google Scholar 

  • Changeux, J. P., Devillers-Thiery, A., and Chemouilli, P. (1984). Acetylcholine receptor: An allosteric protein.Science 2251335–1345.

    Google Scholar 

  • Changeux, J. P., Pinset, C., and Ribera, A. B. (1986). Effects of chlorpromazine and phencyclidine on mouse C2 acetylcholine receptor kinetics.J. Physiol. (Lond.)378497–513.

    Google Scholar 

  • Chiu, S. Y., Mrose, H. E., and Ritchie, J. M. (1979). Anomalous temperature dependence of the sodium conductance in rabiit nerve compared with frog nerve.Nature 279327–328.

    Google Scholar 

  • Criado, M., Eibl, H., and Barrantes, F. J. (1984). Functional properties of the acetylcholine receptor incorporated in model lipid membranes. Differential effects of chain length and head group of phospholipids on receptor affinity states and receptor mediated ion translocation.J. Biol. Chem. 2599188–9198.

    Google Scholar 

  • Dalziel, A. W., Rollins, E. S., and McNamee, M. G. (1980). The effect of cholesterol on agonist induced flux in acetylcholine receptor vesicles.FEBS Lett. 122193–196.

    Google Scholar 

  • De Kruijff, B., Gerritsen, W. J., Oerlemans, A., Demel, R. A., and Van Deenen, L. L. M. (1974). Polyene antibiotic sterol interactions in membranes ofAcholeplasma laidlawii cells and lecithin liposomes. I. Specificity of the membrane permeability changes induced by the polyene antibiotics.Biochim. Biophys. Acta 33930–43.

    Google Scholar 

  • Demel, R. A., and De Kruijff, B. (1976). The function of sterols in membranes.Biochim. Biophys. Acta 457109–132.

    Google Scholar 

  • Fossier, P., Baux, G., and Tauc, L. (1983a). Possible role of acetylcholinesterase in regulation of postsynaptic receptor efficacy at a central inhibitory synapse ofAplysia.Nature 301710–712.

    Google Scholar 

  • Fossier, P., Baux, G., and Tauc, L. (1983b). Direct and indirect effects of an organophosphorus acetylcholinesterase inhibitor and of an oxime on a neuro-neuronal synapse.Pflugers Arch. 39615–22.

    Google Scholar 

  • Fossier, P., Baux, G., and Tauc, L. (1984). Postsynaptic acetylcholine receptor efficacy is similarly increased by detergents and acetylcholinesterase inhibitors at anAplysia synapse.Brain Res. 308369–372.

    Google Scholar 

  • Futerman, A. H., Fiorini, R. M., Roth, E., Low, M. G., and Silman, I. (1985). Physicochemical behaviour and structural characteristics of membrane-bound acetylcholinesterase fromTorpedo electric organ. Effect of phosphatidyl inositol specific phospholipase C.Biochem. J. 226369–377.

    Google Scholar 

  • Gardner, D., and Stevens, C. F. (1980). Rate-limiting step of inhibitory postsynaptic current decay inAplysia buccal ganglia.J. Physiol. (Lond.)304145–164.

    Google Scholar 

  • Giraudat, J., Dennis, M., Heidmann, T., Chang, J. Y., and Changeux, J. P. (1986). Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: Serine 262 of the subunit is labelled by3H-chlorpromazine.Proc. Natl. Acad. Sci. USA 832719–2723.

    Google Scholar 

  • Gotow, T., and Hashimoto, P. H. (1983). Filipin resistance in intermediate junction membranes of guinea pig ependyma: Possible relationship to filamentous underlying.J. Ultrastruct. Res. 8483–93.

    Google Scholar 

  • Heidmann, T., and Changeux, J. L. (1984). Time-resolved photolabeling by the noncompetitive blocker chlorpromazine of the acetylcholine receptor in its transiently open and closed ion channel conformations.Proc. Natl. Acad. Sci. USA 811897–1901.

    Google Scholar 

  • Heron, D. S., Shinitzky, M., Hershkowitz, M., and Samuel, D. (1980). Lipid fluidity markedly modulates the binding of serotonin to mouse brain membranes.Proc. Natl. Acad. Sci. USA 777463–7467.

    Google Scholar 

  • Heron, D., Israeli, M., Hershkowitz, M., Samuel, D., and Shinitzky, M. (1981). Lipid-induced modulation of opiate receptors in mouse brain membranes.Eur. J. Pharmacol. 72361–364.

    Google Scholar 

  • Kehoe, J. (1972). Three acetylcholine receptors inAplysia neurones.J. Physiol. (Lond.)225115–146.

    Google Scholar 

  • Komai, Y., Matsukawa, S., and Satake, M. (1973). Lipid composition of the nervous tissue of the invertebratesAplysia kurodai (gastropod) andCambarus clarki (arthropod).Biochim. Biophys. Acta 316271–281.

    Google Scholar 

  • Leterrier, F., Mendyk, A., and Viret, J. (1976). Interaction of chlorpromazine with biological membranes. A photochemical study using spin labels.Biochem. Pharmacol. 252469–2474.

    Google Scholar 

  • Madden, T. D., Chapman, D., and Quinn, P. J. (1979). Cholesterol modulates activity of calcium dependent ATPase of the sarcoplasmic reticulum.Nature 279538–541.

    Google Scholar 

  • McCaman, R. E., and Dewhurst, S. A. (1971). Metabolism of putative transmitters in individual neurons ofAplysia californica. Acetylcholinesterase and catechol-O-methyl transferase.J. Neurochem. 181329–1335.

    Google Scholar 

  • North, P., and Fleischer, S. (1983). Alteration of synaptic membrane cholesterol/phospholipid ratio using a lipid transfer protein. Effect on aminobutyric acid uptake.J. Biol. Chem. 2581242–1253.

    Google Scholar 

  • Perrelet, A., Garcia-Segura, L. M., Singh, A., and Orci, L. (1982). Distribution of cytochemically detectable cholesterol in the electric organ ofTorpedo marmorata.Proc. Natl. Acad. Sci. USA 792598–2602.

    Google Scholar 

  • Popot, J. L., Demel, R. A., Sobel, A., Van Deenen, L. L. M., and Changeux, J. P. (1978). Interaction of the acetylcholine (nicotinic) receptor protein fromTorpedo marmorata electric organ with monolayers of pure lipids.Eur. J. Biochem. 8527–42.

    Google Scholar 

  • Robenek, H., Jung, W., and Gebhardt, R. (1982). The topography of filipin-cholesterol complexes in the plasma membrane of cultured hepatocytes and their relation to cell junction formation.J. Ultrastruct. Res. 7895–106.

    Google Scholar 

  • Salesse, R., Garnier, J., Leterrier, F., Daveloose, D., and Viret, J. (1982). Modulation of adenylate cyclase activity by the physical state of pigeon erythrocyte membrane. 1. Parallel drug-induced changes in the bilayer fluidity and adenylate cyclase activity.Biochemistry 211581–1586.

    Google Scholar 

  • Sato, M., Maruhashi, J., Yai, H., and Shozushima, M. (1983). Effects of various enzymes and chemical modification reagents on the Na+ and Cl dependent responses of the ganglion cells to acetylcholine.Jap. J. Physiol. 33757–776.

    Google Scholar 

  • Slater, N. T., Hall, A. F., and Carpenter, D. O. (1984). Kinetic properties of cholinergic desensitization inAplysia neurons.Proc. R. Soc. Lond. B 22363–78.

    Google Scholar 

  • Slater, N. T., Hall, A. F., and Carpenter, D. O. (1985). Trifluoperazine and calcium antagonists accelerate cholinergic desensitization inAplysia neurons.Brain Res. 329275–279.

    Google Scholar 

  • Slater, N. T., David, J. A., and Carpenter, D. O. (1986). Relaxation studies on the interaction of hexamethonium with acetylcholine receptor channels inAplysia neurons.Cell. Mol. Neurobiol. 6191–211.

    Google Scholar 

  • Stieger, S., Brodbeck, U., Reber, B., and Brunner, J. (1984). Hydrophobic labeling of the membrane binding domain of acetylcholinesterase fromTorpedo marmorata.FEBS Lett. 168231–234.

    Google Scholar 

  • Storch, J., and Kleinfeld, A. M. (1985). The lipid structure of biological membranes.TIBS 26418–421.

    Google Scholar 

  • Tauc, L., and Gerschenfeld, H. M. (1962). A cholinergic mechanism of inhibitory synaptic transmission in a molluscan nervous system.J. Neurophysiol. 25236–262.

    Google Scholar 

  • Taylor, P., Lwebuga-Mukasa, J., Lappi, S., and Berman, H. A. (1978). Structure of acetylcholinesterase: Its relationship to the postsynaptic membrane. InCholinergic Mechanisms and Psychopharmacology, Advances in Behavioral Biology, Vol. 24 (Jenden, D. J., Ed.), Plenum Press, New York, pp. 239–251.

    Google Scholar 

  • Wiley, J. S., and Cooper, R. A. (1975). Inhibition of cation cotransport by cholesterol enrichment of human red cell membranes.Biochim. Biophys. Acta 413425–431.

    Google Scholar 

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Fossier, P., Baux, G. & Tauc, L. Modulation of an acetylcholine receptor responsiveness by filipin and chlorpromazine studied in neurons ofAplysia californica . Cell Mol Neurobiol 7, 49–59 (1987). https://doi.org/10.1007/BF00734989

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  • DOI: https://doi.org/10.1007/BF00734989

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