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On the mechanism of levosimendan-induced dopamine release in the striatum of freely moving rats

Rocchitta, Gaia Giovanna Maria and Delogu, Maria Rosaria and Migheli, Rossana and Solinas, Luigi and Susini, Giuseppe and Desole, Maria Speranza and Miele, Egidio and Miele, Maddalena and Serra, Pier Andrea (2004) On the mechanism of levosimendan-induced dopamine release in the striatum of freely moving rats. Journal of Pharmacological Sciences, Vol. 95 (3), p. 299-304. eISSN 1347-8648. Article.

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DOI: 10.1254/jphs.FPE04003X


The Ca2+ sensitizer levosimendan (LEV) improves myocardial contractility by enhancing the sensitivity of the contractile apparatus to Ca2+. In addition, LEV promotes Ca2+ entry through L-type channels in human cardiac myocytes. In this study, which was performed using microdialysis, infusion of LEV at 0.25 μM for 160 min increased dopamine (DA) concentrations (up to fivefold baseline) in dialysates from the striatum of freely moving rats. Ca2+ omission from the perfusion fluid abolished baseline DA release and greatly decreased LEV-induced DA release. Reintroduction of Ca2+ in the perfusion fluid restored LEV-induced DA release. Chelation of intracellular Ca2+ by co-infusing 1,2-bis (o-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid tetra (acetoxymethyl) ester (BAPTA-AM, 0.2 mM) did not affect basal DA release and scarcely affected LEV-induced increases in dialysate DA. In addition, co-infusion of the L-type (Cav) 1.1-1.3) voltage-sensitive Ca2+-channel inhibitor nifedipine failed to inhibit LEV-induced increases in dialysate DA, which, in contrast, was inhibited by co-infusion of the N-type (Cav) 2.2) voltage-sensitive Ca2+-channel inhibitor ω-conotoxin GVIA. We conclude that LEV promotes striatal extracellular Ca2+ entry through N-type Ca2+ channels with a consequent increase in DA release.

Item Type:Article
ID Code:274
Uncontrolled Keywords:Levosimendan, microdialysis, striatal dopamine, calcium entry
Subjects:Area 06 - Scienze mediche > MED/41 Anestesiologia
Area 05 - Scienze biologiche > BIO/14 Farmacologia
Divisions:001 Università di Sassari > 03 Istituti > Anestesologia, rianimazione e terapia intensiva
001 Università di Sassari > 01 Dipartimenti > Neuroscienze, scienze materno infantili
Publisher:The Japanese Pharmacological Society
Deposited On:18 Aug 2009 10:01

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