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.
|Number of pages||7|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|Publication status||Published - 1988|
ASJC Scopus subject areas