title: 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-125I]triiodothyronine to calmodulin from pig brain, studied by equilibrium dialysis, was dependent on Ca2+, was saturable and reversible, with an apparent Kd of 2.79 microM and binding capacity of 0.5 nmol/20 micrograms of calmodulin L- and D-thyroxine, D-triiodothyronine and tetrac displaced [L-125I]triiodothyronine at concentrations of 8-10 microM; 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-125I]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 Ca2+-calmodulin, the activation of cyclic AMP phosphodiesterase by the latter is suppressed.
authors.affiliation: Institut für Klinische Biochemie der Universität Bonn, F.R.G.
authors.forename: G S
authors.initials: GS
authors.lastname: Rao
authors.forename: H
authors.initials: H
authors.lastname: Lemoch
authors.forename: C
authors.initials: C
authors.lastname: Cronrath
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism* / Q000494:pharmacology / Q000528:radiation effects; D004347:Drug Interactions; D004789:Enzyme Activation; D007700:Kinetics; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013552:Swine; D013963:Thyroid Hormones / Q000378:metabolism* / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D014284:Triiodothyronine / Q000378:metabolism* / Q000494:pharmacology / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D002147:Calmodulin; D013963:Thyroid Hormones; D014284:Triiodothyronine; D014268:Trifluoperazine; D015105:3',5'-Cyclic-AMP Phosphodiesterases