Actions of nipecotic acid and SKF89976A on GABA transporter in cone-driven horizontal cells dissociated from the catfish retina. 1995

K Takahashi, and S Miyoshi, and A Kaneko, and D R Copenhagen
Department of Physiology, Keio University School of Medicine, Tokyo, Japan.

Whole-cell voltage-clamp recordings were made from dissociated horizontal cells of the catfish retina. In the presence of picrotoxin (PTX, 100 microM), GABA evoked a sustained inward current at negative holding potentials. Dose-response measurements were well fitted by a logistic curve with a Hill coefficient of 1.11 and EC50 of 9.76 microM. When external Na+ was replaced with Li+, this GABA-induced current was eliminated. The substitution of methanesulfonate for Cl- also suppressed the current. This current was blocked by either nipecotic acid or SKF89976A. However, the mechanisms by which these drugs suppress the GABA-induced current differ. Intracellularly applied SKF89976A blocked the GABA-induced current, while nipecotic acid intracellularly had no effect. beta-Alanine at concentrations greater than 1 mM exerted a slight inhibitory effect. Extracellularly applied SKF89976A produced no current by itself but suppressed GABA-induced currents. Dose-response curves showed that SKF89976A has an IC50 of 0.93 microM and a Hill coefficient of 2.68. Nipecotic acid evoked a current response, like GABA. A Hill coefficient was 1.64 and an EC50 was 7.69 microM. This nipecotic acid-induced current was blocked by substituting Li+ for Na+ or by the addition of SKF89976A. This result is consistent with other studies indicating that nipecotic acid is transported in place of GABA. Extracellular Na+ was required for the prolonged suppression by extracellularly applied SKF89976A, while the extracellular Cl- depletion has no influence on the suppression. The pharmacological profile of this GABA transporter fits the neuronal rather than the glial type of cloned transporters.

UI MeSH Term Description Entries
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D009557 Nipecotic Acids Acids, Nipecotic
D011392 Proline A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons. L-Proline,L Proline
D012160 Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the OPTIC NERVE and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the CHOROID and the inner surface with the VITREOUS BODY. The outer-most layer is pigmented, whereas the inner nine layers are transparent. Ora Serrata
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D002397 Catfishes Common name of the order Siluriformes. This order contains many families and over 2,000 species, including venomous species. Heteropneustes and Plotosus genera have dangerous stings and are aggressive. Most species are passive stingers. Eremophilus mutisii,Heteropneustes,Plotosus,Siluriformes,Arius,Catfish,Colombian Catfish,Catfish, Colombian
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005680 gamma-Aminobutyric Acid The most common inhibitory neurotransmitter in the central nervous system. 4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000927 Anticonvulsants Drugs used to prevent SEIZURES or reduce their severity. Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic

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