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 K i of 5 μM). 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.