title: Class II pyrethroids: noninhibitors calcineurin.
abstract: Type II pyrethroid insecticides have been reported to be potent inhibitors of bovine brain calcineurin (EC 3.1.3.16, Enan E and Matsumara F, Biochem Pharmacol 43: 1777-1784, 1992). In concentrations up to 10(-5) M, none of the pyrethroid insecticides used in this study caused inhibition of the calcineurin-dependent dephosphorylation of the 19-amino acid phosphopeptide derived from the regulatory subunit R-II of the cyclic adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase, which has been established as a good substrate for this enzyme. Neither did any of the compounds tested cause a shift in the inhibitory activity of okadaic acid (apparent Ki of 5 microM). The assumption that calcineurin is generally inhibited by pyrethroid insecticides is incorrect, and the interpretation of cellular experiments in which this assumption has been made must be revised.
authors.affiliation: Novartis Pharma Inc., Basel, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Enz
authors.forename: E
authors.initials: E
authors.lastname: Pombo-Villar
mesh_terms: D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007306:Insecticides / Q000494:pharmacology*; D009570:Nitriles; D019319:Okadaic Acid / Q000494:pharmacology; D010748:Phosphopeptides / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011722:Pyrethrins / Q000494:pharmacology*
chemical_list: D002148:Calmodulin-Binding Proteins; D004791:Enzyme Inhibitors; D007306:Insecticides; D009570:Nitriles; D010748:Phosphopeptides; D011722:Pyrethrins; C017160:cypermethrin; D019319:Okadaic Acid; C017180:decamethrin; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; C017690:fenvalerate