Efflux of putative transmitters from superfused rat brain slices induced by low chloride ion concentrations.
Slices of rat cerebral cortex, preloaded with [14C]gamma-aminobutyric acid (GABA) and either [3H]5-hydroxytryptamine (5-HT) or [3H]noradrenaline, were superfused with media in which varying concentrations of Cl- had been replaced with other monovalent anions. Rapid reduction of [Cl-], by superfusion with media containing instead the impermeant anions propionate, isethionate, gluconate, or methyl sulphate, caused increases in the efflux of tritiated biogenic amines, but the increase in that of [14C]-GABA was not significant. The increased efflux of [3H]5-HT evoked by superfusion with low Cl- levels when propionate was the replacement anion, was transient and was linearly related to the log[Cl-]-1. It was not affected by removal of Ca2+ or by addition of 10 mM Mg2+ and was delayed but not abolished by tetrodotoxin. The low Cl(-)-evoked efflux of [3H]5-HT was not affected by pretreatment with neuronal reuptake blockers but was inhibited by picrotoxin, strychnine, and 4-acetamido-4-isothiocyanostilbene-2,2-disulphonic acid and was enhanced by glycine. Muscimol and GABA were without effect. These observations are taken to indicate that the efflux of biogenic amines is brought about by terminal depolarisation due to outward movement of Cl- in low chloride-containing media. They are of relevance to other physiological and pharmacological studies in which anion concentrations are manipulated and suggest that the anion-evoked release phenomenon may provide a model for the analysis of Cl(-)-dependent mechanisms in nerve terminals.
D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000818:Animals; D000838:Anions; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology*; D005260:Female; D005998:Glycine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013331:Strychnine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D000838:Anions; D002118:Calcium; D002712:Chlorides; D005998:Glycine; D018377:Neurotransmitter Agents; D009638:Norepinephrine; D010852:Picrotoxin; D012701:Serotonin; D013331:Strychnine; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid