17β-Estradiol Induces Gastrointestinal Motility Disorder by Decreasing CPI-17 Phosphorylation Via Changes in Rho-Family G-Protein Rnd Expression in Small Intestine
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概要
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In the present study, we investigated the long-term effects of 17β-estradiol on the motility of small intestine in in vitro organ culture and in vivo treatment studies. When rat ileal circular smooth muscle tissues were cultured with 17β-estradiol (0.1 and 1 μM) for 5 days, carbachol-induced contraction was inhibited. In ileal tissue isolated from ovariectomized rat treated with 17β-estradiol (200 μg/kg/day s.c. for 3 days), carbachol-induced contraction was also impaired. Both in vitro and in vivo, 17β-estradiol treatment upregulated heat shock protein 27 (HSP27) expression, indicating the activation of estrogen receptor in the intestinal smooth muscle. 17β-estradiol did not change protein expression levels of RhoA and RhoA-associated coiled coil-forming serine/threonine kinases (ROCKs); however, it upregulated Rnd2 and Rnd3, Rho-family G-proteins that counteract the functions of RhoA, both in vitro and in vivo. In organ culture, treatment of ileal tissue with 17β-estradiol greatly suppressed the carbachol-induced increase in phosphorylation at Thr38 in CPI-17 without altering total CPI-17 protein expression. These results suggest that 17β-estradiol upregulates Rnd expression to inhibit the RhoA-mediated Ca2+ sensitization of contractile mechanisms, which are mediated by CPI-17 phosphorylation in ileal smooth muscle. This mechanism may contribute to the intestinal motility disorder occurring in gender-dependent bowel diseases.
- 社団法人 日本獣医学会の論文
著者
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Hori Masatoshi
Department Of Radiology Graduate School Of Medicine Osaka University
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Hori M
Leaf Tobacco Research Center Japan Tobacco Inc.:(present Address)laboratory Of Insect Science And Bi
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Ozaki Hiroshi
Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences The Universit
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OHAMA TAKASHI
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The Univers
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SHIMOMURA Aya
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The Univers
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Ozaki Hiroshi
Department Of Electronic Engineering Faculty Of Engineering Osaka University
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Ozaki Hiroshi
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo
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SHIMOMURA Aya
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo
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