The so-called anticalmodulins fluphenazine, calmidazolium, and compound 48/80 inhibit the Ca2+- transport system of the endoplasmic reticulum.
We present evidence that a Ca2+- transport system of the endoplasmic reticulum with the "mitotic" Ca2+- ATPase as an essential component is another target for the anticalmodulin drugs fluphenazine, calmidazolium, and compound 48/80. Furthermore we show by affinity chromatography that there is a direct interaction between the solubilized Ca2+- ATPase and fluphenazine. Since the Ca2+- uptake system as well as the solubilized Ca2+- ATPase are calmodulin- free, the effect of fluphenazine, calmidazolium and compound 48/80 may be understood as a result of the interaction between these drugs and the Ca2+- ATPase. We propose that there are calmodulin- like sequences in the molecule of the Ca2+- ATPase. The inhibitory effect of these three drugs can be then explained by their recognition of the calmodulin- like structures.
Wülfroth
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Petzelt
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D001665:Binding Sites; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D004347:Drug Interactions; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D005476:Fluphenazine / Q000494:pharmacology; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D013347:Subcellular Fractions / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D002147:Calmodulin; D007093:Imidazoles; D003189:p-Methoxy-N-methylphenethylamine; C031938:calmidazolium; D000252:Calcium-Transporting ATPases; D005476:Fluphenazine; D002118:Calcium