Action of 4-Amino-2-fluorobutanoic Acid and Other Structural Analogues on Gamma-Aminobutyric Acid Transport by Channel Catfish Brain
| Autor: | Linda A. Malizia, Glenda Crites, Godfrey Tunnicliff |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Tiagabine
Physiology Sodium Biological Transport Active chemistry.chemical_element Nerve Tissue Proteins In Vitro Techniques Sodium Channels GABA Antagonists chemistry.chemical_compound Non-competitive inhibition Chlorides Drug Discovery medicine Nipecotic acid Animals GABA transporter Neurotransmitter gamma-Aminobutyric Acid Brain Chemistry Pharmacology biology Temperature General Medicine Ictaluridae nervous system chemistry Biochemistry Gamma-aminobutyric acid transport biology.protein medicine.drug Catfish |
| Zdroj: | Journal of Basic and Clinical Physiology and Pharmacology. 13 |
| ISSN: | 2191-0286 0792-6855 |
| DOI: | 10.1515/jbcpp.2002.13.3.179 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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