Effects of low extracellular chloride on dopamine release and the dopamine transporter.
Removal of chloride (Cl-) from the superfusion medium results in increased spontaneous efflux of dopamine (DA) but not acetylcholine from rabbit striatal slices prelabeled with [3H]DA and [14C]choline. Cl- was substituted to varying degrees with the impermeant anion, isethionate (IS-), or the permeant anion, nitrate (NO3-). The magnitude of low Cl(-)-induced DA efflux was inversely related to the external [Cl-] and was greater with IS- than with NO3-. Analysis of the composition of the 3H efflux in terms of DA and its metabolites revealed an increase in [3H]DA with decreasing Cl- concentration. Reduction of external Ca++ from 1.3 to 0.13 mM increased low Cl(-)-induced DA efflux. In slices depleted of vesicular DA by reserpine pretreatment and subsequently labeled and superfused in the presence of monoamine oxidase and catechol-O-methyltransferase inhibitors, the same inverse relationship between [Cl-] and spontaneous DA efflux was observed. Neuronal DA uptake inhibitors, nomifensine, mazindol, GBR-12909 and cocaine, all increased the rate of low Cl(-)-induced DA efflux in the reserpinized preparation. Cl(-)-induced DA efflux in untreated and reserpinized preparations was not blocked by tetrodotoxin, amiloride, furosemide, picrotoxin or 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid). Low Cl- inhibited initial rates of [3H]DA uptake. At Cl- concentrations producing significantly different efflux rates (0 and 7.4 mM Cl-, IS- and NO3- substitution), DA uptake was inhibited in all cases by greater than 90%. Additionally, the binding of [3H]mazindol, one of the uptake inhibitors, to striatal membranes was unaffected by removal of Cl-. In summary, low Cl- produces a nonexocytotic rapid outward transport of DA. Extracellular Cl- is not required for the binding to transporter sites or for the inhibition of neuronal uptake produced by neuronal uptake inhibitors.
Diliberto
P A
PA
Division of Clinical Pharmacology, University of North Carolina, Chapel Hill.
Jeffs
R A
RA
Cubeddu
L X
LX
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000494:pharmacology; D002712:Chlorides / Q000502:physiology*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D014179:Neurotransmitter Uptake Inhibitors / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D011954:Receptors, Dopamine / Q000502:physiology; D012110:Reserpine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D002712:Chlorides; D014179:Neurotransmitter Uptake Inhibitors; D011954:Receptors, Dopamine; D013779:Tetrodotoxin; D012110:Reserpine; D000109:Acetylcholine; D002118:Calcium; D004298:Dopamine