2000 Fiscal Year Final Research Report Summary
Modulation of sympathetic nervous system by environmental estrogens : Molecular and pharmacological analysis in adrenal medulla
| Project/Area Number |
11839030
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
TOYOHIRA Yumiko University of Occupational and Environmental Health School of Medicine, Research assistant, 医学部, 助手 (90269051)
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| Co-Investigator(Kenkyū-buntansha) |
UEZONO Yasuhito Nagasaki University School of Medicine, Assistant professor, 医学部, 講師 (20213340)
YANAGIHARA Nobuyuki University of Occupational and Environmental Health School of Medicine, Professor, 医学部, 教授 (80140896)
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| Project Period (FY) |
1999 – 2000
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| Keywords | adrenal medullary cell / noradrenaline transporter / ion channel / nonylphenol / bisphenol A / catecholamine secretion |
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| Research Abstract |
Environmental estrogens are nonsteroidal manmade chemicals that can enter the body by ingestion or absorption and mimic the action of estrogens. Environmental estrogens have been reported to modulate sexual differentiation by interacting with nuclear steroid receptors. The focus has been on reproductive organs, but sex steroids have far more widespread actions. Estrogen has been reported to modulate the function of neurotransmitter receptors, transporters and ionic channels via nongenomic mechanisms. In the present study, to investigate the influence of environmental estrogens on neuro-endocrine system, we examined the effects of bisphenol A and nonylphenol on catecholamine secretion and uptake in cultured bovine adrenal medullary cells.
Bisphenol A significantly inhibited the uptake of [^3H] noradrenaline by the cells in a concentration-dependent manner (1-100 μM). The effect was associated with a decrease in the maximal velocity of the transport process with no significant change in t
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he Michaelis-Menten constant. Treatment of the cells with 17β-estradiol reproduced the inhibitory effects of bisphenol A on the norepinephrine transporter activity. Scatchard analysis of [^3H] desipramine binding revealed that bisphenol A decreased the maximal binding and increased the dissociation constant. Bisphenol A inhibited carbachol-induced catecholamine secretion, ^<45>Ca and ^<22>Na influx in a concentration-dependent manner (10-100 μM). It also inhibited veratridine and high K-induced responses in a concentration-dependent manner. Treatment of the cells with nonylphenol led to a significant inhibition of carbachol-induced catecholamine secretion and ^<45>Ca influx via an activation of nicotinic acetylcholine receptor in a concentration (10-100 μM) - and time (2-72 h) - dependent manner. It also inhibited veratridine-induced responses via an activation of voltage-dependent Na channels, whereas it had little effect on catecholamine secretion caused by high K, a direct activation of voltage-dependent Ca channels.
These results suggest that environmental estrogens modulate the sympathetic nervous activity through inhibition of receptor, ion channel and transporter in non-genomic manner. Less
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[Publications] Kajiwara, K., Yanagihara, N., Ioka, T., Tsutsui, M., Yashiro, A., Toyohira, Y., Nakashima, Y., & Izumi, F.: "Modification of low density lipoprotein potentiates its inhibitory effect on catecholamine secretion in cultured bovine adrenal medullary cells."Naunyn-Schmiedeberg's Archives of Pharmacology. 360. 99-102 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Shibuya, I., Tanaka, K., Uezono, Y., Ueta, Y., Toyohira, Y., Yanagihara, N., Izumi, F.& Yamashita, H.: "Prostaglandin E_2 induces Ca^<2+> relaese from ryanodine/caffeine-sensitive stores in bivine adrenal medullary cells via EP_1-like receptors."Journal of Neurochemistry. 73(5). 2167-2174 (1999)
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[Publications] Yanagihara, N., Utsunomiya, K., Cheah, T.B., Hirano, K., Kajiwara, K., Nakamura, E., Toyohira, Y., Uezono, Y., Ueno, S & Izumi, F.: "Characterization and functional role of leptin receptor in cultured bovine adrenal medullary cells."Biochemical Pharmacology. 59(9). 1141-1145 (2000)
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[Publications] Uryu, K., Minami, K., Yanagihara, N., Hara, K., Toyohira, Y., Izumi, F.& Shigematsu, A.: "Inhibition by neuromuscular blocking drugs of norepinephrine transporter in cultured bovine adrenal medullary cells."Anesthesia & Analgesia. 91(3). 546-551 (2000)
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[Publications] Yoshimura, R., Yanagihara, N., Hara, K., Terao, T., Nakamura, J., Ueno, S., Toyohira, Y., Uezono, Y., Kaneko, S., Kawamura, M., Abe, K.& Izumi, F.: "Inhibitory effects of clazapine and oyher antipsychotic drugs on noradrenaline transporter in cultured bovine adrenal medullary cells."Psychopharmacology. 149. 17-23 (2000)
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[Publications] Utsunomiya, K., Yanagihara, N., Tachikawa, E., Cheah, T.B., Kajiwara, K., Toyohira, Y., Ueno, S.& Izumi, F.: "Stimulation of catecholamine synthesis in cultured bovine adrenal medullary cells by leptin."Journal of Neurochemistry. 76(4). 1652-1661 (2001)
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[Publications] Yoshimura, R., Yanagihara, N., Hara, K., Nakamura, J., Toyohira, Y., Ueno, S.& Izumi, F.: "Dual phases of functional change in norepinephrine transporter in cultured bovine adrenal medullary cells by long-term treatment with clozapine."Journal of Neurochemistry. (in press). (2001)
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[Publications] Shiraishi, S., Shibuya, I., Uezono, Y., Yokoo, H., Toyohira, Y., Yamamoto, R., Yanagita, T., Kobayashi, H.& Wada, A.: "Heterogeneous increases of cytoplasmic calcium : Distinct effects on subunit mRNA leveles."British Journal of Pharmacology. (in press). (2001)
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