Calmodulin antagonists elevate the levels of 32P-labeled polyphosphoinositides in human platelets.

The calmodulin antagonists trifluoperazine, chlorpromazine, perphenazine, promazine, tamoxifen and the naphthalene sulfonamide derivatives W7 and W13 increased the level of 32P-incorporation into human platelet PIP and PIP2. Various drugs with poor anti-calmodulin activity were ineffective. The increase in 32P-PIP and 32P-PIP2 required micromolar concentrations of trifluoperazine and was time-dependent, reaching half-maximal within two minutes of the addition of the drug. These results indicate that the calmodulin antagonists perturb polyphosphoinositide metabolism, probably at the level of the PI- and PIP-kinases and/or the PIP2- and PIP-phosphomonoesterases.