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Benzodiazepinen in perspectief (I): De GABAA-benzodiazepine-receptor

Published online by Cambridge University Press:  18 September 2015

Summary

In this first part of a review on recent insights into the structure and function of the γ-aminobuty rie acid type A - benzodiazepine receptor system, the γ-aminobutyric acid type A (GABAA) receptor and the different types of benzodiazepine (BDZ) receptors known at this moment are dicussed. GABAA- and BDZ receptors are coupled in a supramolecular GABAA-BDZ-ionophore receptor complex, each consisting of five acidic glycoprotein molecules called subunits. These subunits can be classified into five groups: α, β, γ, σ and ρ. Present evidence indicates the existence of multiple subtypes of these subunits. Multiple GABAA-BDZ receptors exist in the brain that show differential distribution and developmental patterns. These receptors differ from their subunit composition. The final functional properties of the receptor are determined by the different subunits constituting this receptor. Heterogeneity among α- subunits may determine the diversity of BDZ pharmacology in different regions of the nervous system.

Type
Research Article
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 1996

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References

Literatuur

1.Sternbach, LH. The discovery of CNS active 1,4-benzodiazepines. In: Costa, E, ed. The Benzodiazepines: From molecular Biology to clinical Practice. New York: Raven Press, 1983: 16.Google Scholar
6.Guidoni, I, Corda, MG, Wise, BC, et al.GABAergic synapses: supramolecular organization and biochemical regulation. Neu-ropharmacol 1983; 22: 1471–9.Google Scholar
7.Lüddens, H, Korpi, ER. Biological function of GABAA/benzo-diazepine receptor heterogeneity. J psychiat Res 1995; 29: 7794.CrossRefGoogle Scholar
10.Zorumski, CF, Iseberg, KE. Insights Into the Structure and Function of GABA-Benzodiazepine Receptors: Ion Channels and Psychiatry. Am J Psychiat 1991; 148: 162–73.Google ScholarPubMed
11.Ticku, MK, Mehta, AK, Kamatchi, GL. GABAA and GABAB receptor pharmacology in cultured spinal cord neurons. Adv biochem Psychopharmacol 1990; 46: 141–51.Google ScholarPubMed
15.Bormann, J, Feigenspan, A. GABAC receptors. TINS 1995; 18: 525–9.Google ScholarPubMed
27.Ticku, JK, Maksay, G. Convulsant/depressant site of action at the allosteric benzodiazepine-GABA receptor complex. Life Sci 1983; 33: 2363–75.CrossRefGoogle Scholar
32.Barnard, EA. The Molecular Biology of GABAA Receptors and their Structural Determinants. In: Biggio, G, Sanna, E, Serra, M, Costa, E, eds. GABAA Receptors and Anxiety. 48th ed. New York: Raven Press, 1995: 116.Google Scholar
35.Sieghart, W. Structure and pharmacology of gamma-aminobuty-ric acid(A) receptor subtypes. Pharmacol Rev 1995; 47: 181234.Google Scholar
44.Haefely, WE. Allosteric modulation of the GABAA receptor channel: a mechanism for interaction with a multitude of central nervous system functions. In: Mohler, H, Da Prada, M, eds. The Challenge of Neuropharmacology: A Tribute to the Memory of Willy Haefely. Basel: Ed Roche, 1994: 1539.Google Scholar
47.Turner, JD, Bodewitz, G, Thompson, CL, Stephenson, FA. Immunohistochemical mapping of gamma-aminobutyric acid type-A receptor alpha subunits in rat central nervous system. In: Stephens, DN, ed. Anxiolytic ß-Carbolines: From molecular Biology to the Clinic. Berlin: Springer-Verlag, 1993: 2949.CrossRefGoogle Scholar
54.Wieland, HA, Luddens, H, Seeburg, PH. Molecular determinants in GABAA/'BZ receptor subtypes. Adv biochem Psychopharmacol 1992; 47: 2940.Google ScholarPubMed
63.Luddens, HLMolecular biology of gamma-aminobutyric acid type A/benzodiazepine receptors. Psychopharmacol Ser 1993; 11: 1628.Google ScholarPubMed
78.Haefely, W, Kulcsar, A, Mohler, H, Pieri, L, Pole, P, Schaffner, R. Possible involvement of GABA in the central ictions of benzo-diazepines. In: Costa, E, Greengard, P, eds. Mechanism of Action of Benzodiazepines. New York: Raven Press, 1975: 131–51.Google ScholarPubMed
86.Pritchett, DB, Luddens, H, Seeburg, PH. Type I and type II GABAA-benzodiazepine receptors produced in transfected cells. Science 1989; 245: 1389–92.CrossRefGoogle ScholarPubMed
88.Gunther, U, Benson, J, Benke, D, et al.Benzodiazepine-insensitive mice generated by targeted disruption of the gamma(2) subunit gene of gamma- aminobutyric acid type A receptors. Proc natl Acad Sci USA 1995; 92: 7749–53.CrossRefGoogle ScholarPubMed
100.Giorgi, O, Lecca, D, Cancedda, E, Serra, GP, Corda, MG. Modulation of [S-35]TBPS binding by ligands with preferential affinity for benzodiazepine BZ(1) sites in the cerebral cortex of newborn and adult rats. Eur J Pharmacol-Molc Pharm 1995; 290: 3747.CrossRefGoogle Scholar
104.Doble, A, Martin, IL. Multiple benzodiazepine receptors - no reason for anxiety. Trends pharmacol Sci 1992; 13: 7681.CrossRefGoogle ScholarPubMed
113.Krueger, KE, Papadopoulos, V. Mitochondrial benzodiazepine receptors and the regulation of steroid biosynthesis. Ann Rev Pharmacol Toxicol 1992; 32: 211–37.CrossRefGoogle ScholarPubMed
117.Ymer, S, Draguhn, A, Wisden, W, et al.Structural and functional characterization of the gamma 1 subunit of GABAA/benzodia-zepine receptors. EMBO J 1990; 9: 3261–7.CrossRefGoogle ScholarPubMed
120.Nielsen, M, Braestrup, C, Squires, RF. Evidence for a late evolutionary appearance of brain-specific benzodiazepine receptors: An investigation of 18 vertebrate and 5 invertebrate species. Brain Res 1978; 141: 342–6.CrossRefGoogle ScholarPubMed
122.Killisch, I, Dotti, CG, Laurie, DJ, Luddens, H, Seeburg, PH. Expression patterns of GABAA receptor subtypes in developing hippocampal neurons. Neuron 1991; 7: 927–36.CrossRefGoogle ScholarPubMed
127.Brooks-Kayal, AR, Pritchett, DB. Developmental changes in human gamma-aminobutyric acid A receptor subunit composition. Ann Neurol 1993; 34: 687–93.CrossRefGoogle ScholarPubMed
128.Greenblatt, DJ, Harmatz, JS, Shader, RI. Clinical pharmacokinetics of anxiolytics and hypnotics in the elderly. Therapeutic considerations (Part I). Clin Pharmacokinet 1991; 21: 165–77.CrossRefGoogle ScholarPubMed
135.Alger, BE, Pitler, TA. Retrograde signaling at GABA(A)-receptor synapses in the mammalian CNS. Trends Neurosci 1995; 18: 333–40.CrossRefGoogle ScholarPubMed