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  • Title: Chloride-dependence of the potency of inhibitors of the neuronal noradrenaline carrier in the rat vas deferens.
    Author: Ungell AL, Oberleithner H, Graefe KH.
    Journal: Naunyn Schmiedebergs Arch Pharmacol; 1989; 339(1-2):65-70. PubMed ID: 2725700.
    Abstract:
    (1) Vasa deferentia obtained from reserpine-pretreated rats were exposed to 0.15 mumol l-1 3H-(-)noradrenaline (with monoamine oxidase and catechol-O-methyltransferase being inhibited) and initial rates of the neuronal 3H-noradrenaline uptake as well as IC50 values for inhibition of uptake by desipramine, cocaine or (-)metaraminol determined at various external Cl- concentrations (0-145 mmol l-1) and a fixed high Na+ concentration (145 mmol l-1). (2) When the Cl- concentration in the medium was decreased neuronal uptake fell. As far as Cl- concentrations ranging from 10 to 145 mmol l-1 are concerned, the dependence of uptake on Cl- obeyed Michaelis-Menten kinetics with an apparent Km and Vmax of 6.2 mmol l-1 and 116 pmol g-1 min-1, respectively. At Cl- concentrations below 10 mmol l-1, uptake was higher than expected from the values of Km and Vmax, and even in the nominal absence of Cl- from the medium a remainder of neuronal uptake was still detectable. Evidence is presented to show that, on incubation at Cl- concentrations below 10 mmol l-1, intracellular Cl- leaks out, so that the actual Cl- concentrations in the extracellular fluid are probably higher than in the medium. (3) The potencies of desipramine and cocaine for inhibition of neuronal uptake were markedly dependent on the Cl- concentration in the medium, but the type of Cl- -dependence differed. While the IC50 for desipramine decreased, that for cocaine increased with increasing Cl- concentration (2-145 mmol l-1).(ABSTRACT TRUNCATED AT 250 WORDS)
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