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Antagonism of estrogen receptor and calmodulin association by antiestrogens is not dependent on an interaction with calmodulin

par Rowlands, Martin G.;Grimshaw, Rachel;Jarman, Michael;Bouhoute, Abdellah ;Leclercq, Guy
Référence Biochemical pharmacology, 53, 2, page (241-244)
Publication Publié, 1997-01

Article révisé par les pairs

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Résumé :

Previously, two antiestrogenic estradiol derivatives (3 and 4) bearing the basic side chain of tamoxifen were shown to impede the binding of the estrogen receptor (ER) to calmodulin (CaM)-Sepharose. In this study, the interaction of these and related compounds with calmodulin was examined using the cyclic AMP phosphodiesterase (cAMP-PDE) assay. Neither of the steroids gave any significant inhibition of the calmodulin dependent cAMP-PDE activity up to a final concentration of 20 μM. For comparison, tamoxifen and nafoxidine produced IC50 values of 6.7 μM ± 1.0 and 7.4 μM ± 1.1, respectively. In addition, a comparison was made of the activity of some triphenylethylene derivatives against CaM dependent cAMP-PDE and the ER-CaM Sepharose assays, but no relationship was observed. Overall, these results demonstrate that inhibition of the ER-CaM association by various steroidal and triphenylethylene antiestrogens does not relate to antagonism of calmodulin function or their binding affinity for the estrogen receptor.