Evidence that the antiestrogen binding site is a histamine or histamine-like receptor.
N,N-diethyl-2-[(4 phenylmethyl)-phenoxy]-ethanamine X HCl (DPPE), a compound selective for the antiestrogen binding site, is structurally similar to the aminoethyl ether group of antihistamines. Our studies now reveal that H1-, but not H2-antagonists, also compete for this site in the order: DPPE = hydroxyzine = perchlorperazine greater than phenyltoloxamine greater than pyrilamine greater than diphenhydramine. The affinity of these compounds for the antiestrogen binding site correlates with their in vitro cytotoxicity against MCF-7 and EVSA-T human breast cancer cells. Tamoxifen, DPPE and hydroxyzine also bind to H1 receptors present in digitonin-solubilized rat liver microsomes, but with less affinity than pyrilamine, which is selective for this site; the ratio of H1 to antiestrogen binding sites in this preparation is 4:1. The data suggest that the antiestrogen binding site may be, in whole or in part, a receptor for histamine different from H1 and H2.
Brandes
L J
LJ
Macdonald
L M
LM
Bogdanovic
R P
RP
D000818:Animals; D001667:Binding, Competitive; D001943:Breast Neoplasms; D002470:Cell Survival / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000378:metabolism / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism; D009376:Neoplasms, Hormone-Dependent; D010647:Phenyl Ethers / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011955:Receptors, Drug; D011960:Receptors, Estrogen / Q000378:metabolism*; D011968:Receptors, Histamine / Q000378:metabolism*; D013629:Tamoxifen / Q000378:metabolism
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D010647:Phenyl Ethers; D011955:Receptors, Drug; D011960:Receptors, Estrogen; D011968:Receptors, Histamine; D013629:Tamoxifen; C043062:tesmilifene