OATP2B1和阿托伐他汀对大鼠比例卟啉异构体的影响

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences Pub Date : 2023-09-14 DOI:10.1016/j.jphs.2023.09.003

Jonny Kinzi , Markus Grube , Janine Hussner , Isabell Seibert , Matthias Hamburger , Henriette E. Meyer zu Schwabedissen

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引用次数: 0

摘要

讨论了共聚卟啉I（CPI）和III（CPIII）作为有机阴离子转运多肽（OATP）的生物标志物。我们报道了野生型、rSlco2b1敲除和SLCO2B1人源化大鼠在基线和给予阿托伐他汀（一种CPIII特异性rOATP2B1/hOATP2B1和CPI/CPIII转运rOATP1B2的抑制剂）后的CPI和CPIII水平。阿托伐他汀对OATP的抑制导致CPI和CPIII血清水平显著升高。然而，rSlco2b1基因敲除动物的基础CP血清水平显著较低（CPI）或未受影响（CPIII）。在阿托伐他汀存在的情况下，这种基因型效应被消除。总之，我们的结果表明OATP2B1对大鼠CP血清水平产生了意想不到的影响。

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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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来源期刊

Journal of pharmacological sciences 医学-药学

CiteScore

6.20

自引率

2.90%

发文量

104

审稿时长

31 days

期刊介绍： 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.