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GABA binding sites: their density, their affinity to muscimol and their behaviour against neuroactive steroids in human gliomas of different degrees of malignancy

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Summary

The aim of the present investigation was to answer the question if there exists a relation between the equipment of human gliomas with GABA binding sites and the degree of malignancy of these tumours diagnostically characterized according to WHO classification. The following parameters were assessed: the density, the affinity and the sensitivity to the modulating steroids 3 α-hydroxy-5 α-pregnane-20-one (3 α OH-DHP) and 3 α,21dihydroxy-5 α-pregnane-20-one (THDOC). Scatchard analysis and non linear computerization revealed that the occurrence of GABA sites was directly related to the degree of tumour malignancy: GABA sites were only detectable in lower malignant gliomas of WHO grade II but not in the very malignant glioblastomas. However, irrespective of the individual density to be detected all glioma GABA sites were sensitive to 3 α-hydroxy-5 α-pregnane-20-one (3 α OH-DHP) and 3 α,21dihydroxy-5 α-pregnane-20-one (THDOC) without exception. The effects of THDOC were due to increases in the number of binding sites whereas in the presence of 3 α OH-DHP a decrease in affinity was noted, additionally. These findings support the view of a normal functional integrity of GABA receptors in gliomas.

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References

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein using the principle of protein-dye binding. Anal Biochem 72: 248–54

    Google Scholar 

  • Butt A, Tutton M (1992) Response of oligodendrocytes to glutamate and gamma-aminobutyric acid in the intact mouse optic nerve. Neurosci Lett 146: 108–110

    Google Scholar 

  • Chvatal A, Kettenman H (1991) Effect of steroids on GABA induced currents in cultured mouse astrocytes. Pflügers Arch 419: 263–266

    Google Scholar 

  • Gee KW (1988) Steroid modulation of the GABA/benzodiazepine receptor-linked chloride ionophore. Mol Neurobiol 2: 291–317

    Google Scholar 

  • Hoppe D, Kettenmann H (1989) GABA triggers a Cl efflux from cultured mouse oligodendrocytes. Neurosci Lett 97: 334–339

    Google Scholar 

  • Jussofie A (1993a) A new highly sensitive procedure-a prerequisite to evaluate the density of GABAA receptors and to study their allosteric properties in distinct areas of rat brain. Biol Chem Hoppe-Seyler 374: 61–8

    Google Scholar 

  • Jussofie A (1993b) Brain region-specific effects of neuroactive steroids on the affinity and density of the GABA binding site. Biol Chem Hoppe-Seyler 374: 265–270

    Google Scholar 

  • Kettenmann H, Backus KH, Schachner M (1987) Gamma-aminobutyric acid opens Cl-channels in cultured astrocytes. Brain Res 404: 1–9

    Google Scholar 

  • Lan NC, Gee KW, Bolger MB, Sheng Chen J (1991) Differential responses of expressed recombinant human gamma-aminobutyric acidA receptors to neurosteroids. J Neurochem 57: 1818–1821

    Google Scholar 

  • Laurie DJ, Seeburg PH, Wisden W (1992) The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. II. Olfactory bulb and cerebellum. J Neurosci 12: 1063–76

    Google Scholar 

  • Majewska MD, Harrison ML, Schwartz RD, Barker JL, Paul SM (1986) Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science 232: 1004–07

    Google Scholar 

  • Olsen RW, Tobin AJ (1990) Molecular biology of GABAA receptors. FASEB J 4: 1469–1480

    Google Scholar 

  • Peters JA, Kirkness EF, Callachan H, Lambert J, Turner AJ (1988) Modulation of the GABAA receptor by depressant barbiturates and pregnane steroids. Br J Pharmacol 94: 1257–69

    Google Scholar 

  • Puia G, Santi MR, Vicini S, Pritchett DB, Purdy RH, Paul SM, Seeburg P, Costa E (1990) Neurosteroids act on recombinant human GABAA receptors. Neuron 4: 759–765

    Google Scholar 

  • Russell DS, Rubinstein LJ (1989) Pathology of tumours of the nervous system, 5th edn. Edward Arnold, London Melbourne Auckland

    Google Scholar 

  • Scatchard G (1949) The attractions of proteins for small molecules and ions. Ann NY Acad Sci 51: 600–72

    Google Scholar 

  • Turner MM, Ransom RW, Yang JS, Olsen RW (1989) Steroid anaesthetics and naturally occurring analogs modulate the gamma-aminobutyric acid receptor complex at a site distinct from barbiturates. J Pharmacol Exp Ther 248: 960–66

    Google Scholar 

  • Van Blankenfeld, Trotter J, Kettenmann H (1990) Expression and developmental regulation of a GABAA receptor in cultured murine cells of the oligodendrocyte lineage. Eur J Neurosci 3: 310–316

    Google Scholar 

  • Wisden W, Laurie DJ, Monyer H, Seeburg PH (1992) The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon. J Neurosci 12: 1040–62

    Google Scholar 

  • Zülich KJ (1979) Histological typing of tumours of the central nervous system In: World Health Organization (eds) International histological classification of tumours, no. 21. WHO, Geneva, pp 11–25

    Google Scholar 

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Jussofie, A., Reinhardt, V. & Kalff, R. GABA binding sites: their density, their affinity to muscimol and their behaviour against neuroactive steroids in human gliomas of different degrees of malignancy. J. Neural Transmission 96, 233–241 (1994). https://doi.org/10.1007/BF01294790

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  • DOI: https://doi.org/10.1007/BF01294790

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