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  • Title: Influence of cocaine and sodium on bretylium uptake by reserpine-treated guinea-pig left atrium.
    Author: García AG, Sánchez-García P.
    Journal: Br J Pharmacol; 1975 Feb; 53(2):247-55. PubMed ID: 1148485.
    Abstract:
    1 The effects of cocaine and sodium on bretylium uptake into sympathetic nerve terminals were investigated in the reserpine-treated guinea-pig left atrium. The ability of bretylium pretreatment to increase the retention of noradrenaline was used as an index of bretylium uptake. Such increased retention has been assessed both by direct measurement and by the ability of tyramine to produce an inotropic response. 2 The restoration of the response to tyramine after incubation with noradrenaline was abolished when the atrium was pretreated with bretylium in the presence of cocaine. When bretylium was added before cocaine, or when alpha-methyl-noradrenaline (not a substrate for monoamine oxidase) was used for incubation, the responses to tyramine were restored in the normal way. 3 Bretylium greatly enhanced the retention of [3-H]-noradrenaline; when bretylium was added in the presence of cocaine, [3-H]-noradrenaline retention was severely impaired. 4 Pretreatment with bretylium in a low-sodium (25 mM) or sodium-free medium significantly decreased the retention of [3-H]-noradrenaline, as compared with the control. 5 Potassium deprivation did not modify the enhanced retention of [3-H]-noradrenaline induced by bretylium pretreatment. 6 Bretylium was released from the nerve terminals by exposure of the preparation to a sodium-free medium or to a solution containing calcium 50 mM, leading to a considerable decrease in [3-H]-noradrenaline retention. 7 The results are consistent with the view that both cocaine and sodium deprivation block the uptake of bretylium by the adrenergic nerve terminals, and that bretylium is probably taken up by a mechanism similar to or identical with the uptake system for noradrenaline and other amines.
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