GABA binding sites: their density, their affinity to muscimol and their behaviour against neuroactive steroids in human gliomas of different degrees of malignancy.
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 alpha-hydroxy-5 alpha-pregnane-20-one (3 alpha OH-DHP) and 3 alpha,21 dihydroxy-5 alpha-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 alpha-hydroxy-5 alpha-pregnane-20-one (3 alpha OH-DHP) and 3 alpha,21 dihydroxy-5 alpha-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 alpha OH-DHP a decrease in affinity was noted, additionally. These findings support the view of a normal functional integrity of GABA receptors in gliomas.
Jussofie
A
A
Institut für Physiologische Chemie, Universitätsklinikum Essen, Federal Republic of Germany.
Reinhardt
V
V
Kalff
R
R
D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D003900:Desoxycorticosterone / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D008566:Membranes / Q000378:metabolism; D009118:Muscimol / Q000493:pharmacokinetics*; D011280:Pregnanolone / Q000494:pharmacology; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D018079:Receptors, GABA; D013256:Steroids; D009118:Muscimol; D003900:Desoxycorticosterone; C009413:tetrahydrodeoxycorticosterone; D011280:Pregnanolone