短鎖脂肪酸の酪酸との交換により硫酸抱合体を輸送する新規肝特異的有機アニオントランスポーターOAT7の同定

• 安西 尚彦

  Dept. Pharmacol. Toxicol., Kyorin Univ. Sch. Med., Tokyo, Japan

• Shin Ho Jung

  Dept. Pharmacol. Toxicol., Kyorin Univ. Sch. Med., Tokyo, Japan

• 金井 好克

  Dept. Pharmacol. Toxicol., Kyorin Univ. Sch. Med., Tokyo, Japan Dept. System Pharmacol., Osaka Univ. Grad. Sch. Med., Osaka, Japan

書誌事項

タイトル別名

• Novel Liver-specific Organic Anion Transporter OAT7 that Operates the Exchange of Sulfate Conjugates for Short Chain Fatty Acid Butyrate.

抄録

The multispecific organic anion transporters in the liver play an important role in the elimination of toxic substances and in the turnover of endogenous biomolecules. In this study, we functionally characterized a novel organic anion transporter OAT7 (SLC22A9) exclusively expressed in human liver. When expressed in Xenopus oocytes, OAT7 mediated high affinity transport of sulfate-conjugated steroid hormones, estrone sulfate (ES) (Km = 8.7 μM) and DHEA sulfate (Km = 2.2 μM), in a sodium independent manner. ES transport mediated by OAT7 was inhibited by negatively charged BSP, ICG and several sulfate-conjugated xenobiotics. In contrast, glucuronide and glutathione conjugates exhibited no inhibitory effects on the OAT7-mediated transport. Immunohistochemical analysis revealed that OAT7 protein was located in the sinusoidal membrane of hepatocytes. We further examined the trans-stimulatory effects of various endogenous organic anions to investigate the driving force for OAT7-mediated transport. Short chain fatty acids trans-stimulated the OAT7-mediated ES uptake by the injection of those cold compounds into the oocytes. Furthermore, OAT7 mediated [¹⁴C]butyrate uptake and [³H]ES efflux in exchange for extracellular butyrate both in Xenopus oocytes and OAT7-stably expressing cells. These results suggest that OAT7 is the liver-specific organic anion transporter using butyrate as a counterion for its transport of steroid sulfates. [J Physiol Sci. 2008;58 Suppl:S22]

収録刊行物

• 日本生理学会大会発表要旨集

  日本生理学会大会発表要旨集 2008 (0), 022-022, 2008

  一般社団法人　日本生理学会

キーワード

• Organic anion transporter
• steroid sulfates
• butyrate
• short chain fatty acids
• SLC22A9

詳細情報

• CRID: 1390001205728535424
• NII論文ID: 130005449292
• DOI: 10.14849/psjproc.2008.0_022_4
• データソース種別:
  • JaLC
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可