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

Brandes, Lorne J.; Bogdanovic, R.Patricia

doi:10.1016/s0006-291x(86)80462-4

Cited by 41 publications

(13 citation statements)

References 8 publications

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“…Tamoxifen also inhibits the growth of MCF 7 mammary carcinoma cells and not all of these effects are reversed by estradiol [30]. Tamoxifen also binds to histamine-like [31] receptors which may be of the H3 type acting as autoinhibitory for histamine secretion [79]. Even though it is hard to make comparisons between species, it may be reasonable to suggest that use of tamoxi fen may have implications for the therapy of a variety of neuroimmunoendocrine syndromes [7,56,57,80].…”

Section: Discussionmentioning

confidence: 99%

Estradiol Augments while Tamoxifen Inhibits Rat Mast Cell Secretion

Vliagoftis

Dimitriadou

Boucher

et al. 1992

Int Arch Allergy Immunol

150

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Mast cells have been studied extensively for their involvement in allergic reactions, where they secrete numerous powerful mediators in response to immunoglobulin E and specific antigens. However, they are also triggered by neuropeptides, they have been found in close contact with neurons, and they are activated in diseases such as angioedema, interstitial cystitis and irritable bowel disease, the prevalence of which is much higher in women. When tested on purified rat peritoneal mast cells, 17β-estradiol augmented secretion of histamine and serotonin, starting at 1 μM and in a dose-dependent manner, whether stimulated by the mast cell secretagogue compound 48/80 or the neuropeptide substance P. However, 17β-estradiol did not augment mast cell secretion stimulated by immunoglobulin E and specific antiserum indicating that immunologic stimulation is under different regulation. Testosterone inhibited secretion induced by compound 48/80. Tamoxifen, an estrogen receptor antagonist used in the treatment of breast cancer, inhibited serotonin and histamine release from purified rat peritoneal mast cells triggered by compound 48/80 or substance P. Tamoxifen also inhibited the increase in intracellular free Ca²⁺ originating from an influx of extracellular Ca²⁺ in response to compound 48/80. Moreover, tamoxifen antagonized the synergistic effect of phorbol myristate and the cation ionophore A23187 on mast cell secretion, suggesting that tamoxifen’s inhibition may be due to regulation of protein kinase C activity. Tamoxifen may, therefore, have a beneficial effect in other neuroimmunoendocrine disorders both through estrogen receptor blockade and inhibition of mast cell secretion.

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Section: Discussionmentioning

confidence: 99%

Estradiol Augments while Tamoxifen Inhibits Rat Mast Cell Secretion

Vliagoftis

Dimitriadou

Boucher

et al. 1992

Int Arch Allergy Immunol

150

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“…Montecatini Terme, Italy, June [1][2][3]1989 In this meeting proteins will be examined in terms of renal physiology and metabolic functions, markers for detecting kidney damage and mechanisms in volved in drug-induced nephrotoxicity. The Sympo sium will have a basic content and a clinical ap proach.…”

Section: Th International Symposium Of Nephrology At Montecatini On mentioning

confidence: 99%

“…A newly synthesized para-diphenylmeth ane derivative, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine-HCl (DPPE), demonstrates antiproliferative effects in vi tro [1] and is antiestrogenic in vivo [2], DPPE binds with high affinity (K; « 50 nmol/1) to the antiestrogen binding site (AEBS) in rat liver microsomes, but not to the estrogen receptor in rat uterine cytosol [3]. Unlike other AEBS ligands, including tamoxifen and phenothiazines, DPPE does not antagonize the action of calmodulin [4] or protein kinase C [5].…”

mentioning

confidence: 99%

A Novel Non-H<sub>1</sub>, Non-H<sub>2</sub> Histamine Antagonist Protects against Cysteamine-induced Duodenal Ulcers in Rats

Glavin

Brandes

1988

Pharmacology

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A newly synthesized para-diphenylmethane derivative, N, N-dιethyl-2-[4-(phenylmethyl)phenoxy]ethanamine-HCl (DPPE), binds with high affinity to the microsomal anti-estrogen binding site (AEBS). Recent data suggest that the DPPE/AEBS binding site is closely related to a novel low-affinity, non-H₁, non-H₂ histamine site which may be associated with a calcium channel. We previously have shown that DPPE markedly reduces stress-induced and ethanol-induced gastric ulcers and attenuates gastric acid secretion. We now show that DPPE also profoundly reduces cysteamine-induced duodenal ulcers in rats.

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“…This resistant clone differed from the parent MCF-7 cells in having no antiestrogen binding sites but was identical to the parent cells with respect to their estrogen receptor content and affinity. Thirdly, Brandes et al [II,12] demonstrated that NN-diethyl-2-[(4-phenylmethyl)phenoxy]ethanamine hydrochloride, a synthetic compound which binds to the antiestrogen-binding site with high affinity but does not bind to the estrogen receptor, inhibited the growth of MCF-7 cells in vitro [11] and of rat uterus in vivo [12]. These findings provide suggestive evi dence that the antiestrogen-binding site may mediate, at least in part, the antiproliferative effect of anti estrogens, although there are some conflicting obser vations [13][14][15],…”

Section: Introductionmentioning

confidence: 99%

Antiestrogen-Binding Sites in 7,12-Dimethylbenz(a)anthracene-Induced Rat Mammary Tumors: Relation to Growth

Hwang

How²

1990

Oncology

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We have detected specific high-affinity binding sites for nonsteroidal antiestrogens in 98% of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors. Since recent studies have suggested that these binding sites may be involved in the regulation of cell growth and proliferation, we attempted to define a possible relationship between the growth of these hormone-dependent tumors and their antiestrogen-binding site content. Rats bearing such tumors were either treated with haloperidol (to increase prolactin secretion and stimulate tumor growth) or oophorectomized (to reduce circulating estrogen concentration and suppress tumor growth). Compared with controls, haloperidol treatment clearly enhanced tumor growth while oophorectomy induced tumor regression, but neither procedure had any effect on the antiestrogen-binding site concentration. Furthermore, tumors which responded to endocrine manipulation had similar antiestrogen-binding site concentrations as tumors which did not respond. We conclude that (1) the alterations in tumor growth induced by these endocrine manipulations are probably not mediated through a change in antiestrogen-binding site concentration, and (2) the tumor concentration of these binding sites is not under estrogen or prolactin control.

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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

Cited by 41 publications

References 8 publications

Estradiol Augments while Tamoxifen Inhibits Rat Mast Cell Secretion

Estradiol Augments while Tamoxifen Inhibits Rat Mast Cell Secretion

A Novel Non-H<sub>1</sub>, Non-H<sub>2</sub> Histamine Antagonist Protects against Cysteamine-induced Duodenal Ulcers in Rats

Antiestrogen-Binding Sites in 7,12-Dimethylbenz(a)anthracene-Induced Rat Mammary Tumors: Relation to Growth

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