Interaction of calmodulin with iodothyronines: effect of iodothyronines on the calmodulin activation of cyclic AMP phosphodiesterase

Abstract The interaction between calmodulin and iodothyronines and the effect of iodothyronines on the calmodulin activation of cyclic AMP phosphodiesterase were investigated. Binding of [ l - 125 I]triiodothyronine to calmodulin from pig brain, studied by equilibrium dialysis, was dependent on Ca 2+ , was saturable and reversible, with an apparent K d of 2.79 μM and binding capacity of 0.5 nmol/20 μg of calmodulin l - and d -thyroxine, d -triiodothyronine and tetrac displaced [ l - 125 I]triiodothyronine at concentrations of 8–10 μM; triac, 3,3'-diiodothyronine and reverse-triiodothyronine were weak displacers. In the presence of the antipsychotic drug trifluoperazine, binding decreased in a dose-related manner. Ultraviolet irradiation of calmodulin in the presence of trifluoperazine reduced the binding of [ l - 125 I]triiodothyronine to calmodulin irreversibly. Calmodulin activation of cyclic AMP phosphodiesterase decreased when iodothyronines were bound to calmodulin; the calmodulin- l -triiodothyronine complex was the most active among the stereoisomers of thyroxine and triiodothyronine. These results suggest that, when triiodothyronine was bound to Ca 2+ -calmodulin, the activation of cyclic AMP phosphodiesterase by the latter is suppressed.