Furosemide action on cerebellar GABA(A) receptors in alcohol-sensitive ANTrats

Furosemide increases the basal tert-[S-35]butylbicyclophosphorothionate ([S -35]TBPS) binding and reverses the inhibition of the binding by gamma-amino butyric acid (GABA) in the cerebellar GABA(A) receptors containing the alph a 6 and beta 2/beta 3 subunits. These effects are less pronounced in the al cohol-sensitive (ANT) than in the alcohol-insensitive (AT) rat line. The di fference between the rat lines in the increase of basal [S-35]TBPS binding was removed after a Longer preincubation with ethylendiaminetetraacetic aci d (EDTA) containing buffer, but long preincubation did not reduce the GABA content of the incubation fluid or remove the difference in GABA antagonism by furosemide. The GABA sensitivity of the [S-35]TBPS binding did not diff er between the rat lines. There was no nucleotide sequence difference in th e beta 2 or beta 3 subunits between the rat lines and similar beta 2/3 subu nit-dependent agonistic actions by methyl-6,7-dimethoxy-4-ethyl-beta-carbol ine-3-carboxylate (DMCM) in the rat lines were detected. The data suggest t hat there are still unknown structural alterations in the cerebellar GABA(A ) receptors between the AT and ANT rat lines, possibly associated with diff erential alcohol sensitivity. (C) 1999 Elsevier Science Inc. All rights res erved.