Carbon monoxide as a regulator of bile canalicular contractility in cultured rat hepatocytes

Yuichi Shinoda, Makoto Suematsu, Yoshiyuki Wakabayashi, Tsuneharu Suzuki, Nobuhito Goda, Shuji Saito, Tokio Yamaguchi, Yuzuru Ishimura*

*この研究の対応する著者

研究成果: Article査読

57 被引用数 (Scopus)

抄録

This study aimed to examine the mechanism(s) by which carbon monoxide (CO), a product of heme oxygenase reaction, controls the contractility of bile canaliculus (BC) in hepatocytes. When BCs associated with the couplet cells in cultured rat hepatocyte suspension were observed using time-lapse video microscopy, they exhibited periodical contractions with a most-probable interval of 6 minutes under our experimental conditions. The addition of 1 μmol/L zinc protoporphyrin IX (ZnPP), a potent inhibitor of heme oxygenase, to the culture medium elicited a 40% shortening of the interval time together with an increase in intracellular calcium concentrations, while the same concentration of iron protoporphyrin IX did not induce such changes. The production of CO, which was 0.5 nmol/h/108 cells in the absence of ZnPP, diminished to less than 0.1 nmol/h/108 cells upon application of ZnPP. The ZnPP-elicited increases in both contractile frequency and intracellular calcium concentrations were attenuated by the addition of 1 μmol/L CO or 50 μmol/L 1,2-bis(2-aminophenoxy) ethane-tetraacetate, a calcium chelator. Clotrimazole or metyrapone, inhibitors of cytochrome P450-dependent monooxygenase activities, also attenuated the ZnPP-induced elevation of the contractile frequency. On the other hand, intracellular cyclic guanosine monophosphate (cGMP) contents were not altered significantly by the application of ZnPP or by CO. These results indicate that CO generated by heme oxygenase controls the BC function by changing intracellular calcium concentrations presumably through a mechanism involving the cytochrome P450 reaction.

本文言語English
ページ(範囲)286-295
ページ数10
ジャーナルHepatology
28
2
DOI
出版ステータスPublished - 1998
外部発表はい

ASJC Scopus subject areas

  • 肝臓学

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