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ORIGINAL ARTICLE

Inhibition of L-Type Ca_v1.2 Ca²⁺ Channels by 2,(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) and 2-[1-(3-Dimethyl-aminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl) Maleimide (Gö6983)

Institut für Pharmakologie und Toxikologie, Technische Universität München, München, Germany

Abstract

Phosphatidylinositol 3-kinase (PI3-K) is involved in physiological processes of cellular proliferation and inflammation and, as postulated recently, in the regulation of L-type Ca²⁺ channels. The latter conclusion arose in part from the inhibitory action of the compound 2,(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), which has been established as a selective PI3-K inhibitor (IC₅₀ = 1.4 µM). Herein we show, however, that LY294002 and an inhibitor of protein kinase C (PKC), 2-[1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl) maleimide (Gö6983), act as direct Ca²⁺-channel inhibitors, with IC₅₀ values of approximately 20 and 10 µM, respectively. Because both drugs are commonly used at concentrations of approximately 10 µM or higher, the interpretation of such experiments is questionable with respect to a regulatory action of PI3-K or PKC on L-type Ca²⁺ channels.

Received for publication August 11, 2004.

Accepted for publication November 9, 2004.

Address correspondence to: Dr. J. W. Wegener, Institut für Pharmakologie und Toxikologie, Technische Universität München, Biedersteiner Str. 29, 80802 München, Germany. E-mail: wegener{at}ipt.med.tu-muenchen.de

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