METHYLMERCURY MODULATES GABA(A) RECEPTOR COMPLEX DIFFERENTIALLY IN RAT CORTICAL AND CEREBELLAR MEMBRANES IN-VITRO

Effects of methylmercury (MetHg) on the specific [H-3]flunitrazepam bi nding were studied in rat cortical and cerebellar P-2-fractions in vit ro. MetHg did not affect significantly the specific [H-3]flunitrazepam binding in unwashed P-2-fraction but increased it marginally (by 16%) at 100 mu M in washed P-2-fraction, in both brain regions. Muscimol ( 3 mu M), a GABA(A) agonist, stimulated the [H-3]flunitrazepam binding by 30% to 50% depending on the brain region. In washed cerebellar memb ranes the enhancing response of muscimol was 10 to 14% lower after pre incubation of the tissue with MetHg but in cerebral cortex MetHg did n ot modulate the muscimol response at all. The results indicate that Me t-Hg may have region specific effects on GABA(A) receptors in vitro an d the effect may depend on the occupational state of the GABA binding domain of the receptor complex.