Membrane events and ionic processes involved in dopamine release from tuberoinfundibular neurons. II. Effect of the inhibition of the Na+-Ca++ exchange by amiloride
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.
- Research Organization:
- Unive. of Naples (Italy)
- OSTI ID:
- 6805328
- Journal Information:
- J. Pharmacol. Exp. Ther.; (United States), Vol. 246:2
- Country of Publication:
- United States
- Language:
- English
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CALCIUM COMPOUNDS
MEMBRANE TRANSPORT
DIURETICS
BIOLOGICAL EFFECTS
DOPAMINE
SECRETION
SODIUM COMPOUNDS
ATP-ASE
CATIONS
CELL MEMBRANES
HYPOTHALAMUS
IN VITRO
INHIBITION
ION EXCHANGE
OUABAIN
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ACID ANHYDRASES
ALKALI METAL COMPOUNDS
ALKALINE EARTH METAL COMPOUNDS
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
BRAIN
CARBOHYDRATES
CARDIAC GLYCOSIDES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
CHARGED PARTICLES
DRUGS
ENZYMES
GLYCOSIDES
HYDROLASES
HYDROXY COMPOUNDS
IONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MEMBRANES
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PHENOLS
PHOSPHOHYDROLASES
POLYPHENOLS
RODENTS
STROPHANTHINS
SYMPATHOMIMETICS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques