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In vitro effects of organophosphorus compounds on calmodulin activity

1991; Wiley; Volume: 11; Issue: 6 Linguagem: Inglês

10.1002/jat.2550110603

1099-1263

I. Pala, P. J. S. Vig, D. Desaiah, A. Srinivasan,

Pesticide and Herbicide Environmental Studies

Abstract In vitro effects of organophosphorus compounds (OP), such as malathion (M), methyl parathion (MP) and ethyl parathion (EP), on calmodulin (CaM) activity and its active conformation were studied to understand the mechanism(s) of neurotoxicity, since CaM is known to regulate Ca 2+ transport and the enzymes involved in signal transduction and nucleotide metabolism. The biological activity of CaM was assessed as a measure of phosphodiesterase (PDE) stimulation. The effect of OP compounds on the active conformation of CaM was determined by studying the binding of fluorescence probes, namely N ‐phenyl‐1‐naphthylamine (NPN), and changes in dansyl‐calmodulin fluorescence. Dansylated calmodulin was also used to study the effect of OP compounds on complex formation between CaM and PDE. All three OP compounds inhibited the CaM activity and its active conformation in a concentration‐dependent manner. Malathion was less effective in comparison to EP and MP, with IC 50 values of 37 μM, 34.5 μM and 32 μM, respectively, for CaM activity. EP and MP significantly altered NPN and dansyl‐calmodulin fluorescence (50 μM concentrations of OP compounds), whereas M did not show any significant effect on NPN fluorescence. All these compounds significantly affected complex formation between the dansylated CaM and PDE. These results suggest that OP compounds may be interacting with CaM, altering its active conformation, and thus may be inhibiting its biological activity.