Inhibition of calmodulin-dependent cyclic nucleotide phosphodiesterase by flunarizine, a calcium-entry blocker |
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Authors: | K Kubo Y Matsuda H Kase K Yamada |
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Institution: | 1. Pharmaceuticals Research Laboratory (1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka-ken 411), Japan;2. Tokyo Research Laboratory (3-6-6 Asahi-cho, Machida, Tokyo 194) of Kyowa Hakko Kogyo Co., Ltd., Japan |
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Abstract: | It has been reported that flunarizine, classified as calcium entry-blockers, is a potent brain protective drug without any heart depressant effect, contrasting with other drugs in this group. This paper presents evidence that through a competitive antagonism against calmodulin, a major intracellular calcium receptor, flunarizine inhibits the calcium X calmodulin-activated phosphodiesterase activity of bovine brain, but not of heart, whereas other calcium-entry blockers and calmodulin antagonists inhibit to the same extent, the activation of the enzyme from the two sources. It could be suggested that some of pharmacological effects by flunarizine and its differences from other calcium-entry blockers may be explained by its interaction with calmodulin. |
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Keywords: | Flunarizine (E)-1-[bis-(4-fluoropheny)methy]-4-(3-phenyl-2-propenyl)piperazine 2HCl CaM calmodulin PDE phosphodiesterase cAMP cyclic adenosine 3′ 5′-monophosphate EGTA ethylene glycol bis(β-aminoethyl ether)-N N N′ N′-tetraacetic acid |
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