Phospholipid-sensitive calcium-dependent protein kinase: inhibition by antipsychotic drugs.

Abstract Phospholipid-sensitive Ca 2+ -dependent protein kinases partially purified from the rat cerebral cortex, pig spleen, and bovine heart were shown to be inhibited, to varying degrees, by several antipsychotic drugs including trifluoperazine, chlorpromazine, fluphenazine, haloperidol, and chlorprothixene and by the local anesthetic dibucaine. None of these drugs were found to have any significant effect on cyclic AMP-dependent and cyclic GMP-dependent protein kinases. Kinetic analysis suggests that the primary effect of the drugs is mediated through a competitive inhibition of enzyme activation by interacting with phosphlipid.

[1]  J. Kuo,et al.  Purification and characterization of guanosine 3':5'-monophosphate-specific phosphodiesterase from guinea pig lung. , 1977, The Journal of biological chemistry.

[2]  Y. Nishizuka,et al.  Inhibitory action of chlorpromazine, dibucaine, and other phospholipid-interacting drugs on calcium-activated, phospholipid-dependent protein kinase. , 1980, The Journal of biological chemistry.

[3]  P. Seeman,et al.  The membrane actions of anesthetics and tranquilizers. , 1972, Pharmacological reviews.

[4]  W. Y. Cheung,et al.  Calmodulin plays a pivotal role in cellular regulation. , 1980, Science.

[5]  Y Nishizuka,et al.  Calcium-dependent activation of a multifunctional protein kinase by membrane phospholipids. , 1979, The Journal of biological chemistry.

[6]  H. Rasmussen Cell Communication, Calcium Ion, and Cyclic Adenosine Monophosphate , 1970, Science.

[7]  M. M. Bradford A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[8]  M. Shoji,et al.  Guanosine cyclic monophosphate-dependent protein kinase from foetal calf heart. Purification, general properties and catalytic subunit. , 1977, The Biochemical journal.

[9]  M. J. Cormier,et al.  Purification of plant calmodulin by fluphenazine-Sepharose affinity chromatography. , 1979, Biochemical and biophysical research communications.

[10]  D. J. Wolff,et al.  Calcium-dependent cyclic nucleotide phosphodiesterase from brain identification of phospholipids as calcium-independent activators. , 1976, Archives of biochemistry and biophysics.

[11]  M. Shoji,et al.  Purification and general properties of guanosine 3':5'-monophosphate-dependent protein kinase from guinea pig fetal lung. , 1976, The Journal of biological chemistry.

[12]  J. H. Wang,et al.  Calmodulin and its role in the second-messenger system. , 1979, Current topics in cellular regulation.

[13]  S. Colowick,et al.  Methods in Enzymology , Vol , 1966 .