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Carbon monoxide as a regulator of bile canalicular contractility in cultured rat hepatocytes
Author(s) -
Shinoda Yuichi,
Suematsu Makoto,
Wakabayashi Yoshiyuki,
Suzuki Tsuneharu,
Goda Nobuhito,
Saito Shuji,
Yamaguchi Tokio,
Ishimura Yuzuru
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510280202
Subject(s) - intracellular , chemistry , heme oxygenase , hepatocyte , contractility , heme , calcium , calcium in biology , biochemistry , zinc protoporphyrin , protoporphyrin , medicine , endocrinology , biology , enzyme , porphyrin , organic chemistry , in vitro
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/10 8 cells in the absence of ZnPP, diminished to less than 0.1 nmol/h/10 8 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.