title: Action of 4-amino-2-fluorobutanoic acid and other structural analogues on gamma-aminobutyric acid transport by channel catfish brain.
abstract: Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in mammalian brain. The synaptic action of GABA is terminated by a sodium- and chloride-linked transport system. The GABA transporter is known as GAT and several isoforms have been identified. Many components of a GABA neurotransmitter system, including a GABA transport system, are present in channel catfish brain. Using a synaptosomal preparation of catfish brain, we examined the kinetics of inhibition of GABA transport by 4-amino-2-fluorobutanoic acid and several other structural analogues of GABA. The transport constant (Kt) for GABA uptake was 4.46 microM, and 4-amino-2-fluorobutanoic acid produced a noncompetitive type of inhibition (Ki = 12.5 microM). The most potent inhibitors were tiagabine (Ki = 0.23 microM) and (R,S)nipecotic acid (Ki = 2.2 microM), both of which exhibited competitive inhibition. Like 4-amino-2-fluorobutanoic acid, homo-beta-proline (Ki = 9.4 microM) inhibited noncompetitively. Other analogues exhibited competitive inhibition. These observations suggest that the GABA transport system in channel catfish is remarkably similar to that in mammalian brain.
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Evansville, IN 47712, USA. gtunnic@iupui.edu
authors.forename: Glenda J
authors.initials: GJ
authors.lastname: Crites
authors.forename: Linda A
authors.initials: LA
authors.lastname: Malizia
authors.forename: Godfrey
authors.initials: G
authors.lastname: Tunnicliff
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002712:Chlorides / Q000378:metabolism; D018756:GABA Antagonists / Q000494:pharmacology*; D007059:Ictaluridae / Q000378:metabolism*; D066298:In Vitro Techniques; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D013696:Temperature; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: C115800:4-amino-2-fluorobutanoic acid; D002712:Chlorides; D018756:GABA Antagonists; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D005680:gamma-Aminobutyric Acid; D012964:Sodium