Antagonistic effect of triphenylethylenic antiestrogens on the association of estrogen receptor to calmodulin.
Binding of (3H)-estradiol labeled estrogen receptor from uterine cytosol to calmodulin was demonstrated by both affinity chromatography and sucrose gradient sedimentation. Triphenylethylene antiestrogens (tamoxifen family) with strong antagonistic activity against the calmodulin-dependent c-AMP phosphodiesterase largely reduced the binding of the receptor. Relevance of this observation with regard to the major antiproliferative activity (cytotoxicity) of these drugs is discussed.
Bouhoute
A
A
Institut Jules Bordet, Service de Médecine, Laboratoire J.C. Heuson de Cancérologie Mammaire et d'Endocrinologie, Brussels, Belgium.
Leclercq
G
G
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D002846:Chromatography, Affinity; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D007536:Isomerism; D007700:Kinetics; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013552:Swine; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014599:Uterus / Q000378:metabolism
D002147:Calmodulin; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; C016601:afimoxifene; C071362:idoxifene; D004958:Estradiol; D002118:Calcium