{"title":"体内给药H2阻滞剂西咪替丁和雷尼替丁可降低大鼠肝微粒体细胞色素P450IID (CYP2D)亚家族的含量及其活性","authors":"Mitsuru Orishiki , Yoshinori Matsuo , Mikio Nishioka , Yoshiyuki Ichikawa","doi":"10.1016/0020-711X(94)90104-X","DOIUrl":null,"url":null,"abstract":"<div><p></p><ul><li><span>1.</span><span><p>1. The effects of <em>in vivo</em> administration of H<sub>2</sub> blockers, cimetidine and ranitidine (0.6 mmol/kg body weight/day, for 5 days), on several <em>P</em>450 isozymes, the <em>P</em>450IID (CYP2D) subfamily, and their monooxygenase activities in rat liver microsomes were investigated.</p></span></li><li><span>2.</span><span><p>2. <em>In vivo</em> administration of cimetidine and ranitidine decreased the contents of <em>P</em>450 isozymes and the activities of <em>P</em>450-linked monooxygenase systems; i.e., benzphetamine <em>N</em>-demethylase, aminopyrine <em>N</em>-demethylase, 7-ethoxycoumarine <em>O</em>-deethylase, debrisoquine 4-hydroxylase and bufuralol 1'-hydroxylase.</p></span></li><li><span>3.</span><span><p>3. The inhibitory effect on the enzymatic activities of the <em>P</em>450IID (CYP2D)-linked monooxygenase systems was studied by Western blot analysis with serum containing antiCYP2D6 IgG, i.e., LKM1 autoantibody. The amount of <em>P</em>450IID (CYP2D) in liver microsomes decreased more remarkably in the group administered ranitidine or cimetidine <em>in vivo</em> than in controls.</p></span></li><li><span>4.</span><span><p>4. The effects of cimetidine and ranitidine on the activities of the <em>P</em>450IID (CYP2D)-linked monooxygenase systems were investigated <em>in vitro</em>. The activities of debrisoquine 4-hydroxylase and bufuralol 1'-hydroxylase were inhibited <em>in vitro</em> by cimetidine or ranitidine at a higher concentration than that on <em>in vivo</em> administration of either H<sub>2</sub> blocker.</p></span></li><li><span>5.</span><span><p>5. The kinetic parameters for cimetidine or ranitidine as to the activities of debrisoquine 4-hydroxylase and bufuralol 1'-hydroxylase in liver microsomes were determined by means of Lineweaver-Burk plots.</p></span></li><li><span>6.</span><span><p>6. The suppressive effects of cimetidine and ranitidine on the activities of the <em>P</em>450IID (CYP2D)-linked monooxygenase systems <em>in vivo</em> were found to be due to a decrease of the content of the <em>P</em>450IID (CYP2D) protein.</p></span></li></ul></div>","PeriodicalId":13733,"journal":{"name":"International Journal of Biochemistry","volume":"26 6","pages":"Pages 751-758"},"PeriodicalIF":0.0000,"publicationDate":"1994-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0020-711X(94)90104-X","citationCount":"9","resultStr":"{\"title\":\"In vivo administration of H2 blockers, cimetidine and ranitidine, reduced the contents of the cytochrome P450IID (CYP2D) subfamily and their activities in rat liver microsomes\",\"authors\":\"Mitsuru Orishiki , Yoshinori Matsuo , Mikio Nishioka , Yoshiyuki Ichikawa\",\"doi\":\"10.1016/0020-711X(94)90104-X\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p></p><ul><li><span>1.</span><span><p>1. The effects of <em>in vivo</em> administration of H<sub>2</sub> blockers, cimetidine and ranitidine (0.6 mmol/kg body weight/day, for 5 days), on several <em>P</em>450 isozymes, the <em>P</em>450IID (CYP2D) subfamily, and their monooxygenase activities in rat liver microsomes were investigated.</p></span></li><li><span>2.</span><span><p>2. <em>In vivo</em> administration of cimetidine and ranitidine decreased the contents of <em>P</em>450 isozymes and the activities of <em>P</em>450-linked monooxygenase systems; i.e., benzphetamine <em>N</em>-demethylase, aminopyrine <em>N</em>-demethylase, 7-ethoxycoumarine <em>O</em>-deethylase, debrisoquine 4-hydroxylase and bufuralol 1'-hydroxylase.</p></span></li><li><span>3.</span><span><p>3. The inhibitory effect on the enzymatic activities of the <em>P</em>450IID (CYP2D)-linked monooxygenase systems was studied by Western blot analysis with serum containing antiCYP2D6 IgG, i.e., LKM1 autoantibody. The amount of <em>P</em>450IID (CYP2D) in liver microsomes decreased more remarkably in the group administered ranitidine or cimetidine <em>in vivo</em> than in controls.</p></span></li><li><span>4.</span><span><p>4. The effects of cimetidine and ranitidine on the activities of the <em>P</em>450IID (CYP2D)-linked monooxygenase systems were investigated <em>in vitro</em>. The activities of debrisoquine 4-hydroxylase and bufuralol 1'-hydroxylase were inhibited <em>in vitro</em> by cimetidine or ranitidine at a higher concentration than that on <em>in vivo</em> administration of either H<sub>2</sub> blocker.</p></span></li><li><span>5.</span><span><p>5. The kinetic parameters for cimetidine or ranitidine as to the activities of debrisoquine 4-hydroxylase and bufuralol 1'-hydroxylase in liver microsomes were determined by means of Lineweaver-Burk plots.</p></span></li><li><span>6.</span><span><p>6. The suppressive effects of cimetidine and ranitidine on the activities of the <em>P</em>450IID (CYP2D)-linked monooxygenase systems <em>in vivo</em> were found to be due to a decrease of the content of the <em>P</em>450IID (CYP2D) protein.</p></span></li></ul></div>\",\"PeriodicalId\":13733,\"journal\":{\"name\":\"International Journal of Biochemistry\",\"volume\":\"26 6\",\"pages\":\"Pages 751-758\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1994-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/0020-711X(94)90104-X\",\"citationCount\":\"9\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Biochemistry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/0020711X9490104X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Biochemistry","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/0020711X9490104X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
In vivo administration of H2 blockers, cimetidine and ranitidine, reduced the contents of the cytochrome P450IID (CYP2D) subfamily and their activities in rat liver microsomes
1.
1. The effects of in vivo administration of H2 blockers, cimetidine and ranitidine (0.6 mmol/kg body weight/day, for 5 days), on several P450 isozymes, the P450IID (CYP2D) subfamily, and their monooxygenase activities in rat liver microsomes were investigated.
2.
2. In vivo administration of cimetidine and ranitidine decreased the contents of P450 isozymes and the activities of P450-linked monooxygenase systems; i.e., benzphetamine N-demethylase, aminopyrine N-demethylase, 7-ethoxycoumarine O-deethylase, debrisoquine 4-hydroxylase and bufuralol 1'-hydroxylase.
3.
3. The inhibitory effect on the enzymatic activities of the P450IID (CYP2D)-linked monooxygenase systems was studied by Western blot analysis with serum containing antiCYP2D6 IgG, i.e., LKM1 autoantibody. The amount of P450IID (CYP2D) in liver microsomes decreased more remarkably in the group administered ranitidine or cimetidine in vivo than in controls.
4.
4. The effects of cimetidine and ranitidine on the activities of the P450IID (CYP2D)-linked monooxygenase systems were investigated in vitro. The activities of debrisoquine 4-hydroxylase and bufuralol 1'-hydroxylase were inhibited in vitro by cimetidine or ranitidine at a higher concentration than that on in vivo administration of either H2 blocker.
5.
5. The kinetic parameters for cimetidine or ranitidine as to the activities of debrisoquine 4-hydroxylase and bufuralol 1'-hydroxylase in liver microsomes were determined by means of Lineweaver-Burk plots.
6.
6. The suppressive effects of cimetidine and ranitidine on the activities of the P450IID (CYP2D)-linked monooxygenase systems in vivo were found to be due to a decrease of the content of the P450IID (CYP2D) protein.
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