EDTA and EGTA stimulate 36Cl- uptake into rat brain synaptoneurosomes.
Addition of EDTA (0.5-10 mM) to rat brain synaptoneurosomes stimulated rapid, concentration-dependent uptake of 36C1-. Chloride uptake stimulated by EDTA was additive with the 36C1- uptake induced by the GABAA agonist, muscimol, and was not blocked by the GABA-antagonist, picrotoxin, the glycine antagonist, strychnine or the loop diuretic, furosemide. However, the chloride transport inhibitor DIDS completely antagonized 36C1- uptake. EDTA-induced 36C1- uptake varied across brain regions as follows: Striatum greater than hippocampus greater than cerebellum greater than tectum greater than cerebral cortex greater than brain stem greater than hypothalamus. EDTA-induced 36C1- uptake was also present in liver tissues. EDTA analogues, EGTA and CDTA, also stimulated uptake. Although the effect of EDTA was dependent on the presence of extravesicular Ca2+ (0.01-10 mM) this action did not appear to be due to Ca2+ chelation since BAPTA, arsenazo III and citrate were ineffective. These results suggest that EDTA stimulates 36C1- uptake into brain synaptoneurosomes by a picrotoxin-insensitive, calcium-dependent mechanism that may involve a DIDS sensitive anion exchanger or ion channel.
Mathew
J
J
Department of Medical Pharmacology & Toxicology, Texas A&M University College of Medicine, College Station 77843-1114.
Frye
G D
GD
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D002713:Chlorine; D004492:Edetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D009118:Muscimol / Q000494:pharmacology; D011868:Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
D002614:Chelating Agents; D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D011868:Radioisotopes; D009118:Muscimol; C005390:CDTA; D002713:Chlorine; D004533:Egtazic Acid; D004492:Edetic Acid; D002118:Calcium