Cloning and functional expression of a Drosophila gamma-aminobutyric acid receptor.

Article date: 1994/6/21

PubMed ID: 1314944

Journal name: Proceedings of the National Academy of Sciences of the United States of America (ISSN: 0027-8424)


A cDNA encoding a functional gamma-aminobutyric (GABA)-activated Cl- channel has been isolated from an adult Drosophila head cDNA library. When expressed in Xenopus laevis oocytes, the subunit functions efficiently, presumably as a homooligomeric complex and is activated by GABA or muscimol. GABA-evoked currents are highly sensitive to antagonism by picrotoxin but are insensitive to bicuculline, RU 5135, or zinc. Pentobarbitone greatly enhances GABA-evoked currents, whereas the neurosteroid 5 alpha-pregnan-3 alpha-ol-20-one demonstrates a large reduction in both the potency and maximal effect when compared with its actions upon vertebrate GABA type A receptors. Although zinc-insensitive, the subunit is also insensitive to flunitrazepam. Hence, the GABA receptors formed by this subunit exhibit a unique pharmacology when compared with vertebrate GABA type A receptors or those composed of rho subunits. Because the receptor-channel complex functions as a homooligomer, this subunit may be of value in mutagenesis studies aiming to define drug-binding sites.

Author List: Chen R, Belelli D, Lambert J J, Peters J A, Reyes A, Lan N C

Publication Types: Comparative Study; Journal Article

Substances mentioned in the article: Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Convulsants; DNA Primers; DNA, Complementary; Macromolecular Substances; Receptors, GABA; Receptors, GABA-A; Picrotoxin; Muscimol; gamma-Aminobutyric Acid; Flunitrazepam; tert-butylbicyclophosphorothionate; Pentobarbital; Bicuculline;

Mesh terms: Amino Acid Sequence; Animals; Base Sequence; Bicuculline/pharmacology; Bridged Bicyclo Compounds/pharmacology; Bridged Bicyclo Compounds, Heterocyclic; Cloning, Molecular; Convulsants/pharmacology; DNA Primers; DNA, Complementary/analysis; Drosophila melanogaster/genetics; Female; Flunitrazepam/pharmacology; Gene Expression; Macromolecular Substances; Molecular Sequence Data; Muscimol/pharmacology; Oocytes/drug effects; Pentobarbital/pharmacology; Picrotoxin/pharmacology; Polymerase Chain Reaction; Receptors, GABA/biosynthesis; Receptors, GABA-A/physiology; Transcription, Genetic; Xenopus laevis; gamma-Aminobutyric Acid/pharmacology;

Citations: - 1376242

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