CLASS-II PYRETHROIDS - NONINHIBITORS CALCINEURIN

Type II pyrethroid insecticides have been reported to be potent inhibi tors 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 inh ibition of the calcineurin-dependent dephosphorylation of the 19-amino acid phosphopeptide derived from the regulatory subunit R-II of the c yclic adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase, w hich has been established as a good substrate for this enzyme. Neither did any of the compounds tested cause a shift in the inhibitory activ ity of okadaic acid (apparent K-i of 5 mu M). The assumption that calc ineurin is generally inhibited by pyrethroid insecticides is incorrect , and the interpretation of cellular experiments in which this assumpt ion has been made must be revised. (C) 1997 Elsevier Science Inc.