Interaction of DDT and pyrethroids with calmodulin and its significance in the expression of enzyme activities of phosphodiesterase.

To understand the significance of the inhibitory action of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and pyrethroid insecticides on calmodulin, a universal Ca2+ binding protein, a bovine heart phosphodiesterase-calmodulin system was studied. It was found that, at concentrations of less than 10(-5) M, the inhibitory action of DDT of the phosphodiesterase was due entirely to its action on calmodulin alone. Cypermethrin was less potent than DDT, but it also affected only calmodulin. Permethrin was the most potent inhibitor affecting calmodulin and, to a lesser extent, phosphodiesterase. The inhibitory action of these insecticides on calmodulin raises a possibility that many unsuspected Ca2+-related systems are being affected by these insecticidal chemicals, as calmodulin is known to play vital roles in many biological reactions dependent upon Ca2+. These include modulation of phosphodiesterase, neurotransmitter release, adenylate cyclase, Ca2+-dependent protein kinase, myosine light chain kinase and various membrane phosphorylation systems.