ACTIVATION OF PHOSPHOINOSITIDE PROTEIN-KINASE-C PATHWAY IN RAT-BRAIN TISSUE BY PYRETHROIDS

We have investigated the effects of a type II pyrethroid insecticide, deltamethrin, on changes in the protein phosphorylation pattern associated with neurotransmitter release in rat brain synaptosomal preparations. Deltamethrin was found to stimulate directly the activity of the protein kinase C/phosphoinositide pathway at very low concentrations. This action resulted in an increase in the intracellular concentration of inositol 1,4,5-triphosphate (IP3) and free calcium, as well as an increase in overall and specific protein phosphorylation within the synapse. Particularly noticeable was the deltamethrin-induced increase in phosphorylation on two very acidic proteins (87 and 48 kDa proteins) and one basic 38 kDa protein. These results are consistent with those of a previously reported study in which deltamethrin caused an increase in neurotransmitter release which was accompanied by increased intrasynaptosomal free Ca2+ levels and protein phosphorylation activities. Together all these observations support the view that calcium-sensitive proteins involving synaptic transmission are the major action targets of type II pyrethroids.