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

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)286-295
Number of pages10
JournalHepatology
Volume28
Issue number2
DOIs
Publication statusPublished - 1998
Externally publishedYes

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Carbon Monoxide
Bile
Hepatocytes
Heme Oxygenase (Decyclizing)
Bile Canaliculi
Calcium
Cytochrome P-450 Enzyme System
Clotrimazole
Metyrapone
Video Microscopy
Ethane
Cyclic GMP
Mixed Function Oxygenases
Culture Media
zinc protoporphyrin
Cultured Cells
Suspensions

ASJC Scopus subject areas

  • Hepatology

Cite this

Shinoda, Y., Suematsu, M., Wakabayashi, Y., Suzuki, T., Goda, N., Saito, S., ... Ishimura, Y. (1998). Carbon monoxide as a regulator of bile canalicular contractility in cultured rat hepatocytes. Hepatology, 28(2), 286-295. https://doi.org/10.1002/hep.510280202

Carbon monoxide as a regulator of bile canalicular contractility in cultured rat hepatocytes. / Shinoda, Yuichi; Suematsu, Makoto; Wakabayashi, Yoshiyuki; Suzuki, Tsuneharu; Goda, Nobuhito; Saito, Shuji; Yamaguchi, Tokio; Ishimura, Yuzuru.

In: Hepatology, Vol. 28, No. 2, 1998, p. 286-295.

Research output: Contribution to journalArticle

Shinoda, Y, Suematsu, M, Wakabayashi, Y, Suzuki, T, Goda, N, Saito, S, Yamaguchi, T & Ishimura, Y 1998, 'Carbon monoxide as a regulator of bile canalicular contractility in cultured rat hepatocytes', Hepatology, vol. 28, no. 2, pp. 286-295. https://doi.org/10.1002/hep.510280202
Shinoda, Yuichi ; Suematsu, Makoto ; Wakabayashi, Yoshiyuki ; Suzuki, Tsuneharu ; Goda, Nobuhito ; Saito, Shuji ; Yamaguchi, Tokio ; Ishimura, Yuzuru. / Carbon monoxide as a regulator of bile canalicular contractility in cultured rat hepatocytes. In: Hepatology. 1998 ; Vol. 28, No. 2. pp. 286-295.
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