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.
abstract: 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 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.
authors: Institute of Pharmacology, 2nd School of Medicine, University of Naples, Italy.
authors: M
authors: M
authors: Taglialatela
authors: S
authors: S
authors: Amoroso
authors: G
authors: G
authors: Kaparos
authors: F
authors: F
authors: Maurano
authors: G F
authors: GF
authors: Di Renzo
authors: L
authors: L
authors: Annunziato
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009627:Nomifensine / Q000494:pharmacology; D010042:Ouabain / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium; D014700:Verapamil / Q000494:pharmacology
chemical_list: D007473:Ion Channels; D014316:Tritium; D009627:Nomifensine; D013779:Tetrodotoxin; D010042:Ouabain; D004317:Doxorubicin; D014700:Verapamil; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium; D004298:Dopamine