Jonny Kinzi , Markus Grube , Janine Hussner , Isabell Seibert , Matthias Hamburger , Henriette E. Meyer zu Schwabedissen
{"title":"OATP2B1和阿托伐他汀对大鼠比例卟啉异构体的影响","authors":"Jonny Kinzi , Markus Grube , Janine Hussner , Isabell Seibert , Matthias Hamburger , Henriette E. Meyer zu Schwabedissen","doi":"10.1016/j.jphs.2023.09.003","DOIUrl":null,"url":null,"abstract":"<div><p>Coproporphyrin I (CPI) and III (CPIII) are discussed as biomarkers for organic anion transporting polypeptides (OATPs). We report on CPI and CPIII levels in <em>wildtype</em>, <em>rSlco2b1</em>-knockout, and <em>SLCO2B1</em>-humanized rats at baseline and after administration of atorvastatin, an inhibitor of the CPIII-specific rOATP2B1/hOATP2B1 and the CPI/CPIII-transporting rOATP1B2. OATP-inhibition by atorvastatin leads to significantly increased CPI and CPIII serum levels. However, basal CP serum levels in <em>rSlco2b1</em>-knockout animals were significantly lower (CPI), or unaffected (CPIII). In the presence of atorvastatin, this genotype effect was abolished. In conclusion, our results indicate an unexpected impact of OATP2B1 on CP serum levels in rats.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The influence of OATP2B1 and atorvastatin on coproporphyrin isomers in rats\",\"authors\":\"Jonny Kinzi , Markus Grube , Janine Hussner , Isabell Seibert , Matthias Hamburger , Henriette E. Meyer zu Schwabedissen\",\"doi\":\"10.1016/j.jphs.2023.09.003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Coproporphyrin I (CPI) and III (CPIII) are discussed as biomarkers for organic anion transporting polypeptides (OATPs). We report on CPI and CPIII levels in <em>wildtype</em>, <em>rSlco2b1</em>-knockout, and <em>SLCO2B1</em>-humanized rats at baseline and after administration of atorvastatin, an inhibitor of the CPIII-specific rOATP2B1/hOATP2B1 and the CPI/CPIII-transporting rOATP1B2. OATP-inhibition by atorvastatin leads to significantly increased CPI and CPIII serum levels. However, basal CP serum levels in <em>rSlco2b1</em>-knockout animals were significantly lower (CPI), or unaffected (CPIII). In the presence of atorvastatin, this genotype effect was abolished. In conclusion, our results indicate an unexpected impact of OATP2B1 on CP serum levels in rats.</p></div>\",\"PeriodicalId\":16786,\"journal\":{\"name\":\"Journal of pharmacological sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2023-09-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of pharmacological sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1347861323000567\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of pharmacological sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1347861323000567","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
The influence of OATP2B1 and atorvastatin on coproporphyrin isomers in rats
Coproporphyrin I (CPI) and III (CPIII) are discussed as biomarkers for organic anion transporting polypeptides (OATPs). We report on CPI and CPIII levels in wildtype, rSlco2b1-knockout, and SLCO2B1-humanized rats at baseline and after administration of atorvastatin, an inhibitor of the CPIII-specific rOATP2B1/hOATP2B1 and the CPI/CPIII-transporting rOATP1B2. OATP-inhibition by atorvastatin leads to significantly increased CPI and CPIII serum levels. However, basal CP serum levels in rSlco2b1-knockout animals were significantly lower (CPI), or unaffected (CPIII). In the presence of atorvastatin, this genotype effect was abolished. In conclusion, our results indicate an unexpected impact of OATP2B1 on CP serum levels in rats.
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Journal of Pharmacological Sciences (JPS) is an international open access journal intended for the advancement of pharmacological sciences in the world. The Journal welcomes submissions in all fields of experimental and clinical pharmacology, including neuroscience, and biochemical, cellular, and molecular pharmacology for publication as Reviews, Full Papers or Short Communications. Short Communications are short research article intended to provide novel and exciting pharmacological findings. Manuscripts concerning descriptive case reports, pharmacokinetic and pharmacodynamic studies without pharmacological mechanism and dose-response determinations are not acceptable and will be rejected without peer review. The ethnopharmacological studies are also out of the scope of this journal. Furthermore, JPS does not publish work on the actions of biological extracts unknown chemical composition.
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