GABA BINDING-SITES - THEIR DENSITY, THEIR AFFINITY TO MUSCIMOL AND THEIR BEHAVIOR AGAINST NEUROACTIVE STEROIDS IN HUMAN GLIOMAS OF DIFFERENT DEGREES OF MALIGNANCY

The aim of the present investigation was to answer the question if the re exists a relation between the equipment of human gliomas with GABA binding sites and the degree of malignancy of these tumours diagnostic ally characterized according to WHO classification. The following para meters were assessed: the density, the affinity and the sensitivity to the modulating steroids 3 alpha-hydroxy-5 alpha-pregnane-20-one (3 al pha OH-DHP) and 3 alpha,21dihydroxy-5 alpha-pregnane-20-one (THDOC). S catchard analysis and non linear computerization revealed that the occ urrence of GABA sites was directly related to the degree of tumour mal ignancy: GABA sites were only detectable in lower malignant gliomas of WHO grade II but not in the very malignant glioblastomas. However, ir respective of the individual density to be detected all glioma GABA si tes were sensitive to 3 alpha-hydroxy-5 alpha-pregnane-20-one (3 alpha OH-DHP) and 3 alpha 21dihydroxy-5 alpha-pregnane-20-one (THDOC) witho ut 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.