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

M. Taglialatela, S. Amoroso, G. Kaparos, F. Maurano, G. F. Di Renzo, L. Annunziato

Research output: Contribution to journalArticlepeer-review


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 μM). Removal of Ca++ ions from the extracellular space in the presence of the Ca++-chelator ethylene glycol bis(β-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 μM) and nitrendipine (50 μM), two organic antagonists of the voltage-operated channel for Ca++ ions, failed to affect ouabain-induced [3H]DA release. By contrast, adriamycin (100-300 μM), 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 the 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.

Original languageEnglish
Pages (from-to)682-688
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number2
Publication statusPublished - 1988

ASJC Scopus subject areas

  • Pharmacology


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