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Title: Membrane events and ionic processes involved in dopamine release from tuberoinfundibular neurons. I. Effect of the inhibition of the Na+,K+-adenosine triphosphatase pump by ouabain

In the present study we investigated the membrane events and the ionic processes which mediate the stimulatory effect of ouabain on the release of endogenous dopamine (DA) and previously taken-up (3H)DA release from rat hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons. Ouabain (0.1-1 mM) dose-dependently stimulated endogenous DA and newly taken-up (3H)DA release. This effect was counteracted partially by nomifensine (10 microM). Removal of Ca++ ions from the extracellular space in the presence of the Ca++-chelator ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid prevented completely ouabain-elicited (3H)DA release. Lanthanum (1 mM) and cobalt (2 mM), two inorganic Ca++-entry blockers, were able to inhibit this stimulatory effect, whereas verapamil (10 microM) and nitrendipine (50 microM), two organic antagonists of the voltage-operated channel for Ca++ ions, failed to affect ouabain-induced (3H)DA release. By contrast, adriamycin (100-300 microM), a putative inhibitor of cardiac Na+-Ca++ antiporter, dose-dependently prevented ouabain-induced (3H)DA release from TIDA neurons. Finally, tetrodotoxin reduced digitalis-stimulated (3H)DA release. In conclusion, these results seem to be compatible with the idea that the inhibition of Na+,K+-adenosine triphosphatase by ouabain stimulates the release of (3H)DA from a central neuronal system like the TIDA tract and that this effect is critically dependent on the entrance of Ca++ ions into themore » nerve terminals of these neurons. In addition the Na+-Ca++ exchange antiporter appears to be the membrane system which transports Ca++ ions into the neuronal cytoplasm during Na+,K+-adenosine triphosphatase inhibition. The enhanced intracellular Ca++ availability triggers DA release which could occur partially through a carrier-dependent process.« less
Authors:
; ; ; ; ;
Publication Date:
OSTI Identifier:
6805347
Resource Type:
Journal Article
Resource Relation:
Journal Name: J. Pharmacol. Exp. Ther.; (United States); Journal Volume: 246:2
Research Org:
Univ. of Naples (Italy)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CALCIUM COMPOUNDS; MEMBRANE TRANSPORT; DOPAMINE; SECRETION; OUABAIN; BIOLOGICAL EFFECTS; ATP-ASE; CATIONS; CELL MEMBRANES; COBALT; DOSE-RESPONSE RELATIONSHIPS; DOXORUBICIN; HYPOTHALAMUS; IN VITRO; INHIBITION; LANTHANUM; NERVE CELLS; PORINS; RATS; RESPONSE MODIFYING FACTORS; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ACID ANHYDRASES; ALKALINE EARTH METAL COMPOUNDS; AMINES; ANIMAL CELLS; ANIMALS; ANTI-INFECTIVE AGENTS; ANTIBIOTICS; ANTINEOPLASTIC DRUGS; AROMATICS; AUTONOMIC NERVOUS SYSTEM AGENTS; BODY; BRAIN; CARBOHYDRATES; CARDIAC GLYCOSIDES; CARDIOTONICS; CARDIOVASCULAR AGENTS; CELL CONSTITUENTS; CENTRAL NERVOUS SYSTEM; CHARGED PARTICLES; DRUGS; ELEMENTS; ENZYMES; GLYCOSIDES; HYDROLASES; HYDROXY COMPOUNDS; IONS; ISOTOPE APPLICATIONS; LABELLED COMPOUNDS; MAMMALS; MEMBRANE PROTEINS; MEMBRANES; METALS; NERVOUS SYSTEM; NEUROREGULATORS; ORGANIC COMPOUNDS; ORGANS; PHENOLS; PHOSPHOHYDROLASES; POLYPHENOLS; PROTEINS; RARE EARTHS; RODENTS; SOMATIC CELLS; STROPHANTHINS; SYMPATHOMIMETICS; TRANSITION ELEMENTS; VERTEBRATES 550201* -- Biochemistry-- Tracer Techniques