Block by Phytoestrogens of Recombinant Human Neuronal Nicotinic Receptors

Abstract

Abstract. The effects of phytoestrogens on neuronal nicotinic acetylcholine receptor / channels were examined by expressing recombinant channels in Xenopus oocytes. When functional channels were expressed with human a 4 and b2 subuints, daidzein (10 and 100 m M) partially inhibited the ionic current activated by acetylcholine. The current inhibition was also observed when functional channels were expressed with human a3 and b4 subunits or rat homologues. Genistin (100 m M) also inhibited the acetylcholine-activated current. Tamoxifen (100 mM), an antiestrogen did not antagonize the inhibition by daidzein. The results suggest that phytoestrogens, like estrogens and xenoestrogens, block human neuronal acetylcholine receptors through non-genomic mechanisms.

Reusable Floating-Electrode Sensor for the Quantitative Electrophysiological Monitoring of a Nonadherent Cell

“…Significantly, we utilized only a single FES device to measure the effect of various regulating drugs such as genistin, daidzein, and tamoxifen on the nAChR activity of multiple SCLC cells, which enabled a statistically meaningful quantitative analysis without errors from device-to-device variations. The results indicate that the treatment of inhibitors such as genistin and daidzein can dramatically reduce Ca 2+ influx in SCLC cells as expected . Furthermore, tamoxifen, which has been known as the antagonist, was found to only partly block the binding of daidzein to nAChRs.…”

“…Phytoestrogens are known as inhibitors that have a high affinity with α4 nAChRs and inhibit the receptors from interacting with nicotine . Thus, when nicotine is added, Ca 2+ influx through α4 nAChRs is blocked and we should observe a reduced overall Ca 2+ influx into the SCLC cell. , In turn, this decrease of membrane depolarization could also reduce the gate-opening of voltage-gated Ca 2+ channels and additional influx of Ca 2+ . In the case of a partial blocking, the quantitative monitoring of electrophysiological responses can enable the quantitative analysis of the effect of drugs.…”

Chronic exposure to estrogen and the tobacco carcinogen NNK cooperatively modulates nicotinic receptors in small airway epithelial cells

“…It has thus been shown that treatment of ovariectomized rats with estrogen upregulated both mRNA and protein of the ␣4 subunit in the hypothalamus [36] and that estradiol potentiated the ␣4␤2nAChR expressed in Xenopus oocytes or human embryonic kidney cells [37]. By contrast phytoestrogens significantly inhibited the function of the ␣4␤2nAChR expressed in X. oocytes [38]. Recent studies by PCR analysis have shown that the ␣4nAChR subunit gene was downregulated in human lung adenocarcinoma tissues, most of which were collected from women [12].…”

Mechanisms of Cancer Induction by Tobacco-Specific NNK and NNN

“…In turn, the release of GABA is regulated by α4β2nAChR, which is desensitized in smokers [110,111] and additionally downregulated in PACs by NNK, leading to a deficit in GABA [112]. The desensitization of this receptor is enhanced by estrogens and phyto-oestrogens [113]. The predominance of PAC in women and NNK-induced tumors in OGG knockout female mice may therefore, at least in part, be the result of estrogen impaired α4β2nAChR function.…”