Transport of gamma-aminobutyrate and L-glutamate into synaptic vesicles. Effect of different inhibitors on the vesicular uptake of neurotransmitters and on the Mg2(+)-ATPase.
The uptakes of gamma-aminobutyrate (GABA) and L-glutamate into synaptic vesicles isolated from rat brain were compared with respect to the effects of 4-acetamido-4'-isothiocyanostilbene-2,2'- disulphonic acid (SITS), 4,4'-di-isothiocyanostilbene-2,2'-disulphonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino)benzoic acid (N144), agents known to block anion channels. The uptake of glutamate was inhibited by low micromolar concentrations of SITS, DIDS and N144. GABA uptake was much less sensitive to these agents than was glutamate uptake. SITS and N144 inhibited the vacuolar H(+)-ATPase of synaptic vesicles to a smaller extent than the glutamate uptake. The uptake of GABA was not affected by the permeant anions Cl- and Br-, whereas the uptake of glutamate was highly stimulated by low concentrations of these ions. The uptakes of both glutamate and GABA were inhibited by similar, but not identical, concentrations of the lipophilic anion SCN-.
Norwegian Defence Research Establishment, Division for Environmental Toxicology, Kjeller.
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D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000838:Anions; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism*; D002458:Cell Fractionation / Q000379:methods; D005033:Ethylmaleimide / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009579:Nitrobenzoates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012492:Salts; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013861:Thiocyanates / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000838:Anions; D005971:Glutamates; D018377:Neurotransmitter Agents; D009579:Nitrobenzoates; D012492:Salts; D013861:Thiocyanates; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D005680:gamma-Aminobutyric Acid; D000110:Acetylcholinesterase; D017301:Ca(2+) Mg(2+)-ATPase; D005033:Ethylmaleimide; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; C009941:potassium thiocyanate