Estradiol augments while tamoxifen inhibits rat mast cell secretion.
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, 17 beta-estradiol augmented secretion of histamine and serotonin, starting at 1 microM and in a dose-dependent manner, whether stimulated by the mast cell secretagogue compound 48/80 or the neuropeptide substance P. However, 17 beta-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.
Vliagoftis
H
H
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, New England Medical Center, Boston, Mass 02111.
Dimitriadou
V
V
Boucher
W
W
Rozniecki
J J
JJ
Correia
I
I
Raam
S
S
Theoharides
T C
TC
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D013739:Testosterone / Q000494:pharmacology
D011960:Receptors, Estrogen; D013629:Tamoxifen; D012701:Serotonin; D013739:Testosterone; D004958:Estradiol; D011493:Protein Kinase C; D002118:Calcium