Inhibition of L-type Cav1.2 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 (Go6983).
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 Ca(2+) 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 (IC(50) = 1.4 microM). 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 (Go6983), act as direct Ca(2+)-channel inhibitors, with IC(50) values of approximately 20 and 10 microM, respectively. Because both drugs are commonly used at concentrations of approximately 10 microM or higher, the interpretation of such experiments is questionable with respect to a regulatory action of PI3-K or PKC on L-type Ca(2+) channels.
Welling
A
A
Institut für Pharmakologie und Toxikologie, Technische Universität München, Biedersteiner Str. 29, 80802 München, Germany.
Hofmann
F
F
Wegener
J W
JW
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009025:Morpholines / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002867:Chromones; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C465664:2-(1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl)-3-(1H-indol-3-yl)maleimide; C419385:L-type calcium channel alpha(1C); C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one