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.