Pyrimidine-2,4,6-triones are a new class of voltage-gated L-type Ca(2+) channel activators.
Articolo
Data di Pubblicazione:
2014
Abstract:
Cav1.2 and Cav1.3 are the main L-type Ca2þ channel subtypes in the brain. Cav1.3 channels have recently been implicated in the pathogenesis of Parkinson’s disease. Therefore, Cav1.3-selective blockers are developed as promising neuroprotective drugs. We studied the pharmacological properties of a pyrimidine-2,4,6-trione derivative (1-(3-chlorophenethyl)-3- cyclopentylpyrimidine-2,4,6-(1H,3H,5H)-trione, Cp8) recently reported as the first highly selective Cav1.3 blocker. Here we show, in contrast to this previous study, that Cp8 reproducibly
increases inward Ca2þ currents of Cav1.3 and Cav1.2 channels expressed in tsA-201 cells by slowing activation, inactivation and enhancement of tail currents. Similar effects are also observed for native Cav1.3 and Cav1.2 channels in mouse chromaffin cells, while non-Ltype
currents are unaffected. Evidence for a weak and non-selective inhibition of Cav1.3 and Cav1.2 currents is only observed in a minority of cells using Ba2þ as charge carrier. Therefore, our data identify pyrimidine-2,4,6-triones as Ca2þ channel activators.
Tipologia CRIS:
03A-Articolo su Rivista
Keywords:
canali del calcio di tipo L; calcio agonisti; Calcio antagonisti
Elenco autori:
Ortner NJ;Bock G;Vandael DH;Mauersberger R;Draheim HJ;Gust R;Carbone E;Tuluc P;Striessnig J
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