New evidence that the antiestrogen binding site may be a novel growth-promoting histamine receptor (?H3) which mediates the antiestrogenic and antiproliferative effects of tamoxifen.
Using as a probe [3H]-DPPE (N,N-diethyl-2-[(4-phenylmethyl)phenoxy]ethanamine HCl), a novel compound selective for the antiestrogen binding site (AEBS), new evidence is presented that this site could be a growth-promoting histamine receptor of a type not previously described (?H3). In the rat uterus, DPPE alone at a concentration of 4 mg/kg acts as an estrogen antagonist, unlike TAM alone which is a partial estrogen agonist. In the presence of exogenous estradiol, both TAM and DPPE are partial antagonists. This suggests that the "antiestrogenic" effects of tamoxifen are mediated through AEBS/?H3 while the estrogenic effects are mediated through ER.
D000818:Animals; D001667:Binding, Competitive; D001681:Biological Assay; D002927:Cimetidine / Q000378:metabolism; D005260:Female; D006919:Hydroxyzine / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism*; D010052:Ovariectomy; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D011738:Pyrilamine / Q000378:metabolism; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D011968:Receptors, Histamine / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000378:metabolism*; D014599:Uterus / Q000187:drug effects
D010714:Phosphatidylethanolamines; D011960:Receptors, Estrogen; D011968:Receptors, Histamine; D013629:Tamoxifen; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; D006919:Hydroxyzine; D002927:Cimetidine; D011738:Pyrilamine