Article
Chemistry, Analytical
Abdulaziz Ahmed A. Saad, Fan Zhang, Moath Refat, Eyad Abdulwhab H. Mohammed, Mingkang Zhang, Yuyue Chen, Bandar Al Hamyari, Jameel Alafifi, Xin'an Wu
Summary: This study evaluated the effect of tamsulosin on the pharmacokinetics of metformin and found that tamsulosin can increase the systemic exposure and reduce excretion of metformin, possibly through inhibiting Oct2 and Mate1-mediated transport.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2022)
Article
Biochemistry & Molecular Biology
Tatsuya Kawasaki, Chisa Kaneko, Ryosuke Nakanishi, Yoshinori Moriyama, Tomohiro Nabekura
Summary: This study investigated the transport characteristics of amiloride by human MATE1 and found that MATE1 transported amiloride at an extracellular pH of 7.4, with saturated uptake and a bell-shaped pH profile. Additionally, the study discovered that pyrimethamine and fampridine exhibited strong inhibition on MATE1.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Engineering, Environmental
Kwang-Hee Shin, Kyeong-Ryoon Lee, Min-Ji Kang, Yoon-Jee Chae
Summary: In this study, we aimed to identify flavone derivatives that can strongly inhibit OCT2 transport. Among 80 tested flavonoids, 24 showed moderate to strong inhibitory effects on OCT2 activity. Ten of these compounds had IC50 values of less than 5 μM. All 10 compounds alleviated cisplatin-induced cytotoxicity in cells expressing OCT2, with the effectiveness varying depending on the functional moieties in each position. The methyl group at the R1 position and methoxy group at the R6 position of the flavonol backbone were found to be important for OCT2 inhibition.
CHEMICAL ENGINEERING JOURNAL
(2023)
Review
Pharmacology & Pharmacy
Abdulaziz Ahmed A. Saad, Fan Zhang, Eyad Abdulwhab H. Mohammed, Xin'an Wu
Summary: OCT2 and MATE1/2-K are crucial transporters in the kidneys that play a significant role in drug metabolism, therapeutic efficacy, and toxicity. Understanding the localization and functionality of these transporters is essential for preventing or enhancing drug-induced nephrotoxicity.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2022)
Article
Pharmacology & Pharmacy
Kyle Z. Pasquariello, Jason M. Dey, Jason A. Sprowl
Summary: Cisplatin is an effective anticancer drug, but its use is limited by dose-limiting toxicities, including irreversible hearing loss. The mechanism behind cisplatin-induced ototoxicity is not fully understood, but it relies on the presence of specific membrane transporters for cellular accumulation. Targeting these transporters therapeutically has shown success in alleviating cisplatin-induced hearing loss and presents opportunities for mitigating other platinum-induced toxicities.
MOLECULAR PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Hong Yang, Shiwei Zhou, Dong Guo, Obinna N. Obianom, Qing Li, Yan Shu
Summary: The regulation of OCTs and MATEs remains poorly characterized. This study found that Cd2+ and candesartan may regulate OCTs and MATEs through different cellular trafficking pathways, significantly affecting drug disposition in the liver and kidney.
Article
Chemistry, Analytical
Jieyu Zhang, Yan Chen, Wenxiang Fan, Linnan Li, Yueming Ma, Zhengtao Wang, Rong Shi, Li Yang
Summary: The combined efficacy of Plantago asiatica L. seed and Coptis chinensis Franch. rhizoma is better than either herb alone, likely due to herb-herb interactions affecting potency. The active components in Plantago, geniposidic acid (GPA), acteoside (ACT), and plantagoamidinic acid A (PLA), and the active component in Coptis, berberine (BBR), were found to have competitive interactions driven by transporters rOCT2 and rMATE1. These interactions affect the transport and excretion of compounds and lead to changes in efficacy after co-administration.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Pharmacology & Pharmacy
Naotoshi Yamamura, Tsuyoshi Mikkaichi, Ken-Ichi Itokawa, Misa Hoshi, Katja Damme, Stefanie Geigner, Christine Baumhauer
Summary: The aim of this study was to investigate the involvement of transporters in the renal secretion and absorption of mirogabalin. The results showed that mirogabalin is not a substrate of LAT1 but is associated with PEPT1, PEPT2, OAT1, OAT3, OCT2, MATE1, and/or MATE2-K.
Article
Biochemistry & Molecular Biology
Kyra-Elisa Maria Redeker, Ole Jensen, Lukas Gebauer, Marleen Julia Meyer-Toennies, Juergen Brockmoeller
Summary: The human organic cation transporter 1 (OCT1) plays a crucial role in hepatic uptake of organic cations. Recent studies suggest that OCT1 can also transport neutral and anionic substrates, but with lower activity. Understanding the substrate spectrum and transport mechanisms of OCT1, including organic anions, is essential for a comprehensive understanding of its clinical relevance.
Article
Biochemistry & Molecular Biology
David A. Doetsch, Salim Ansari, Ole Jensen, Lukas Gebauer, Christof Duecker, Jurgen Brockmoeller, Alexandra Sachkova
Summary: This study characterized the substrate spectrum of a proton-organic cation (H + OC) antiporter, which is responsible for transporting organic cations through membranes. Using hCMEC/D3 cells as a model, the researchers examined the uptake of 72 drugs and identified 37 of them as good substrates of the H + OC antiporter. Further analysis showed that the substrates had specific characteristics, such as being more hydrophobic and having a lower topological polar surface area.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Joseph L. Jilek, Kayla L. Frost, Kevyn A. Jacobus, Wenxi He, Erica L. Toth, Michael Goedken, Nathan J. Cherrington
Summary: The study found that NASH-induced changes in transporter expression in the liver and kidneys may affect the metabolism and toxicity of CDDP in rats, leading to reduced nephrotoxicity and increased hepatic accumulation of CDDP. Alterations in renal and hepatic transporter expression in NASH rats may play a role in the clearance and sequestration of CDDP.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Neurosciences
Jinan Li, Chang Liu, Samuel Kaefer, Mariam Youssef, Bo Zhao
Summary: Studies have shown that genetically disrupting mechanotransduction in mice partially protects hair cells from cisplatin-induced hair cell death, and functional mechanotransduction is required for the uptake of cisplatin in murine hair cells. Additionally, the otoprotective effects of cimetidine do not require mechanotransduction, suggesting that both the mechanotransduction channel and the organic cation transporter are critical for cisplatin ototoxicity in murine hair cells.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Marta Kantauskaite, Anna Hucke, Beatrice Snieder, Giuliano Ciarimboli
Summary: The study investigates the role of angiotensin II (AII) signaling and hOCT2 in the development of CDDP nephrotoxicity. It is found that AII stimulates hOCT2 function via PKC activation and worsens CDDP cytotoxicity by binding to AT1R. The findings suggest that the AII signaling pathway may play a role in CDDP nephrotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Irene Hernandez-Lozano, Severin Mairinger, Michael Sauberer, Johann Stanek, Thomas Filip, Thomas Wanek, Giuliano Ciarimboli, Nicolas Tournier, Oliver Langer
Summary: The study investigated the role of cation transporters (OCTs, MATEs) in the renal and hepatic disposition of [C-11]metoclopramide in mice. Results showed that OCT1/2 contribute to kidney and liver uptake, while MATEs play a role in urinary excretion of the drug. Cation transporters may contribute to variability in metoclopramide pharmacokinetics and side effects.
PHARMACEUTICAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Keisuke Okamoto, Fumi Kitaichi, Yoshitaka Saito, Hinata Ueda, Katsuya Narumi, Ayako Furugen, Masaki Kobayashi
Summary: Cisplatin is a widely used anticancer drug, but its nephrotoxicity is a significant adverse effect. Studies have shown that multiple doses of Cisplatin can upregulate the expression of renal transporters such as P-gp, and that ascorbic acid may attenuate kidney injury and oxidative stress caused by Cisplatin.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)