In the present study we investigated the effect of amiloride, a rather specific inhibitor of the membrane Na+-Ca++ exchange system, on the release of endogenous dopamine (DA) and 'previously taken-up' [3H]DA from tuberoinfundibular dopaminergic neurons. Amiloride (300 μM) stimulated either endogenous DA or [3H]DA release. Amiloride-induced stimulation of [3H]DA release was prevented in a Ca++-free plus ethylene glycol bis(β-aminoethyl ether)-N,N'-tetraacetic acid medium. Amiloride, at the same concentration, reinforced both high K+- and electrically-induced stimulation of [3H]DA release. These results are explained on the basis of ability of amiloride in blocking the Na+-Ca++ exchange system, therefore causing an elevation of intracellular Ca++ levels in resting conditions, and a further accumulation of Ca++ ions after high K+- or electrically elicited opening of voltage-operated channels specific for Ca++ ions. The enhanced intracellular Ca++ availability may trigger the stimulation of neurotransmitter release. In addition, amiloride was able to block in a dose-dependent manner (70-300 μM) the ouabain-induced [3H]DA release, suggesting that, when intracellular concentrations of Na+ are increased by the blockade of Na+, K+-adenosine triphosphatase the Na+-Ca(+;+) exchange carrier reverses its resting mode of operation, mediating the influx of extracellular Ca++ ions. Amiloride, by blocking the Na+-Ca++ exchange mechanism, prevents the ouabain-elicited entrance of extracellular Ca++ ions, therefore inhibiting [3H]DA release stimulated by the cardioactive glycoside. Collectively, the results of the present study seem to be compatible with the idea that the Na+-Ca++ exchange mechanism is involved in the regulation of [3H]DA release from tuberoinfundibular dopaminergic neurons, through the regulation of Ca++ movements across the plasma membrane.
|Number of pages||6|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|Publication status||Published - 1988|
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