Carbon monoxide as a regulator of bile canalicular contractility in cultured rat hepatocytes
Carbon monoxide as a regulator of bile canalicular contractility in cultured rat hepatocytes
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一氧化碳作为培养大鼠肝细胞胆小管收缩力的调节剂
作者：
Y. Shinoda;M. Suematsu;Y. Wakabayashi;Tsuneharu Suzuki;N. Goda;Shuji Saito;Tokio Yamaguchi;Y. Ishimura
本研究旨在探讨血红素加氧酶反应产物一氧化碳(CO)控制肝细胞胆小管(BC)收缩的机制(S)。用延时视频显微镜观察培养的大鼠肝细胞悬液中结合成对细胞的BCS时，在我们的实验条件下，它们表现出周期性收缩，最大可能间隔6分钟。加入1μ摩尔/L锌原卟啉IX(一种有效的血红素加氧酶抑制剂)可使细胞内钙离子浓度增加40%，间隔时间缩短40%，而相同浓度的铁原卟啉IX对此无明显影响。加入锌后，CO的产生量由无锌时的0.5nmol/h/108个细胞减少到不到0.1nmol/h/108个细胞。加入1μ摩尔/L CO或50μ摩尔/L的1，2-双(2-氨基苯氧基)乙烷-四乙酸酯(钙离子螯合剂)，可减弱锌锌盐引起的收缩频率和细胞内钙离子浓度的增加。细胞色素P450依赖的单加氧酶活性的抑制剂克霉唑或美曲拉酮也减弱了由锌PP引起的收缩频率的升高。另一方面，细胞内环鸟苷一磷酸(CGMP)含量不受锌处理和一氧化碳处理的影响。这些结果表明，由血红素加氧酶产生的CO通过改变细胞内钙离子浓度来控制BC的功能，可能是通过参与细胞色素P450反应的机制。
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.
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原卟啉调节 AtT-20 垂体细胞中的电压门控 Ca 电流。
影响因子：
2.5
作者：
Linden,DJ;Narasimhan,K;Gurfel,D
通讯作者：
Gurfel,D
DOI：
10.1073/pnas.78.9.5362
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
CAPDEVILA, J;CHACOS, N;ESTABROOK, RW
通讯作者：
ESTABROOK, RW
使用显微光学面积测量法定量评估分离的肝细胞对中胆管胆汁的形成。
DOI：
10.1172/jci113919
发表时间：
1989
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Gautam,A;Ng,OC;Strazzabosco,M;Boyer,JL
通讯作者：
Boyer,JL
花生四烯酸的细胞色素 P-450 代谢：“环氧合酶”衍生的类二十烷酸的形成和生物作用。
影响因子：
21.1
作者：
Fitzpatrick,FA;Murphy,RC
通讯作者：
Murphy,RC
一氧化氮通过抑制肌醇三磷酸依赖性钙动员来阻止胆小管收缩。
影响因子：
29.4
作者：
Dufour,JF;Turner,TJ;Arias,IM
通讯作者：
Arias,IM