title: Furosemide action on cerebellar GABA(A) receptors in alcohol-sensitive ANT rats.
abstract: Furosemide increases the basal tert-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding and reverses the inhibition of the binding by gamma-aminobutyric acid (GABA) in the cerebellar GABA(A) receptors containing the alpha6 and beta2/beta3 subunits. These effects are less pronounced in the alcohol-sensitive (ANT) than in the alcohol-insensitive (AT) rat line. The difference between the rat lines in the increase of basal [35S]TBPS binding was removed after a longer preincubation with ethylendiaminetetraacetic acid (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 [35S]TBPS binding did not differ between the rat lines. There was no nucleotide sequence difference in the beta2 or beta3 subunits between the rat lines and similar beta2/3 subunit-dependent agonistic actions by methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) in the rat lines were detected. The data suggest that there are still unknown structural alterations in the cerebellar GABA(A) receptors between the AT and ANT rat lines, possibly associated with differential alcohol sensitivity.
authors.affiliation: Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland. riikka.makela@ktl.fi
authors.forename: R
authors.initials: R
authors.lastname: Mäkelä
authors.forename: M
authors.initials: M
authors.lastname: Uusi-Oukari
authors.forename: S S
authors.initials: SS
authors.lastname: Oja
authors.forename: H
authors.initials: H
authors.lastname: Alho
authors.forename: I
authors.initials: I
authors.lastname: Anghelescu
authors.forename: C
authors.initials: C
authors.lastname: Klawe
authors.forename: H
authors.initials: H
authors.lastname: Lüddens
authors.forename: E R
authors.initials: ER
authors.lastname: Korpi
mesh_terms: D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001386:Azides / Q000378:metabolism / Q000494:pharmacology; D001569:Benzodiazepines / Q000378:metabolism / Q000494:pharmacology; D001640:Bicuculline / Q000378:metabolism / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism / Q000494:pharmacology; D002243:Carbolines / Q000378:metabolism / Q000494:pharmacology; D002531:Cerebellum / Q000737:chemistry / Q000187:drug effects*; D004338:Drug Combinations; D005260:Female; D005665:Furosemide / Q000378:metabolism / Q000494:pharmacology*; D018755:GABA Agonists / Q000378:metabolism / Q000494:pharmacology; D018756:GABA Antagonists / Q000378:metabolism / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D011724:Pyridazines / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D001386:Azides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002243:Carbolines; D004338:Drug Combinations; D018755:GABA Agonists; D018756:GABA Antagonists; D008024:Ligands; D011724:Pyridazines; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D012965:Sodium Chloride; C037476:tert-butylbicyclophosphorothionate; D005665:Furosemide; C042957:Ro 15-4513; C049853:gabazine; D001640:Bicuculline