Effect of Organochlorine and Organotin Compounds on Active Conformation of Calmodulin

Abstract

The interaction of organotin and organochlorine compounds with calmodulin was studied in order to elucidate whether these compounds interact with calmodulin thereby affecting its active conformation. The conformational changes in calmodulin were studied by using N‐phenyl‐1‐naphthylamine (NPN) and dansyl‐calmodulin as fluorescent probes. Chlordecone, an organochlorine compound, suppressed the increase in fluorescence of NPN by complex formation with calmodulin in the presence of Ca²⁺ and the effect was concentration dependent with IC₅₀ of 9.25 μM. However, no effect was observed in the presence of 1 mM EGTA. Other organochlorine compounds such as aldrin, dieldrin, endrin and isodrin even at high concentrations (80 μM) did not affect the Ca²⁺‐dependent change in calmodulin conformation. Chlordecone (20 μM) also inhibited the Ca²⁺‐dependent increase in dansyl‐calmodulin fluorescence. This chlordecone‐induced, conformationally changed calmodulin (involving the high affinity Ca²⁺‐binding sites) was unable to form a Ca²⁺‐dependent complex with phosphodiesterase. Unlike, chlordecone, organotin compounds such as tributyltin (TBT) and triethyltin (TET) increased the NPN fluorescence with ED₅₀ of 5.2 and 175 μM respectively. This effect was Ca²⁺‐dependent. Trimethyltin did not affect NPN fluorescence both in the presence and absence of Ca²⁺. TBT also increased Ca²⁺‐dependent dansyl‐calmodulin fluorescence in a concentration dependent manner. These data suggest that not all compounds interact directly with calmodulin. Chlordecone and TBT alter the active conformation of calmodulin by interacting at different sites on calmodulin.

Notes

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