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.
D001792:Blood Platelets / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002746:Chlorpromazine / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D010546:Perphenazine / Q000494:pharmacology; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000097:blood* / Q000378:metabolism; D011395:Promazine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D013449:Sulfonamides; C037178:phosphatidylinositol 4-phosphate; D013629:Tamoxifen; D014268:Trifluoperazine; C017967:W 7; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide; D010546:Perphenazine; D011395:Promazine; D002746:Chlorpromazine