On the Mechanism of Levosimendan-Induced Dopamine Release in the Striatum of Freely Moving Rats

• Published in: Journal of Pharmacological Sciences 2004, Vol.95(3), pp.299-304
• Main Authors: Rocchitta, Gaia, Delogu, M. Rosaria, Migheli, Rossana, Solinas, Luigi, Susini, Giuseppe, Desole, Maria S., Miele, Egidio, Miele, Maddalena, Serra, Pier Andrea
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Calcium Channels, L-Type - metabolism; Calcium Channels, N-Type - metabolism; calcium entry; Chromatography, High Pressure Liquid; Corpus Striatum - metabolism; Dopamine - biosynthesis; Dopamine - metabolism; Dopamine Agonists - pharmacology; Hydrazones - pharmacology; levosimendan; Male; Microdialysis; Pyridazines - pharmacology; Rats; Rats, Wistar; Simendan; striatal dopamine; Time Factors
• ISSN: 1347-8613; 1347-8648
• 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.