title: Membrane events and ionic processes involved in dopamine release from tuberoinfundibular neurons. II. Effect of the inhibition of the Na+-Ca++ exchange by amiloride.
abstract: 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 microM) 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(beta-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 the 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 microM) 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.
authors.affiliation: Institute of Pharmacology, 2nd School of Medicine, University of Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Taglialatela
authors.forename: S
authors.initials: S
authors.lastname: Amoroso
authors.forename: L M
authors.initials: LM
authors.lastname: Canzoniero
authors.forename: G F
authors.initials: GF
authors.lastname: Di Renzo
authors.forename: L
authors.initials: L
authors.lastname: Annunziato
mesh_terms: D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D005260:Female; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007474:Ion Exchange; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010042:Ouabain / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014316:Tritium
chemical_list: D014316:Tritium; D010042:Ouabain; D000584:Amiloride; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium; D004298:Dopamine