ArticleBritish journal of pharmacology2016
Aristolochic acid, a plant extract used in the treatment of pain and linked to Balkan endemic nephropathy, is a regulator of K2P channels.
Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Properties of Approved Antitumour Chinese Herbal Medicines: Integrating Evidence and Tradition.Drug design, development and therapy · 2026Review
- K2P channels as emerging therapeutic targets for pain: insights from functional studies and transcriptomic analyses.Frontiers in pharmacology · 2026Review
- Skullcapflavone II, a novel NQO1 inhibitor, alleviates aristolochic acid I-induced liver and kidney injury in mice.Acta pharmacologica Sinica · 2023Article
- KCNK3 inhibits proliferation and glucose metabolism of lung adenocarcinoma via activation of AMPK-TXNIP pathway.Cell death discovery · 2022Article
- Structural Insights into the Mechanisms and Pharmacology of KJournal of molecular biology · 2021Review
- Block of TREK and TRESK K2P channels by lamotrigine and two derivatives sipatrigine and CEN-092.Biochemistry and biophysics reports · 2021Article
- The Polysite Pharmacology of TREK KAdvances in experimental medicine and biology · 2021Article
- Effects of the ventilatory stimulant, doxapram on human TASK-3 (KCNK9, K2P9.1) channels and TASK-1 (KCNK3, K2P3.1) channels.Acta physiologica (Oxford, England) · 2020Article
- PIPInternational journal of molecular sciences · 2020Article
- Recent developments in detoxication techniques for aristolochic acid-containing traditional Chinese medicines.RSC advances · 2020Review
- Pharmacologically reversible, loss of function mutations in the TM2 and TM4 inner pore helices of TREK-1 K2P channels.Scientific reports · 2019Article
- Two-pore domain potassium channels: emerging targets for novel analgesic drugs: IUPHAR Review 26.British journal of pharmacology · 2019Review
- Systematic Overview of Aristolochic Acids: Nephrotoxicity, Carcinogenicity, and Underlying Mechanisms.Frontiers in pharmacology · 2019Review
- GI-530159, a novel, selective, mechanosensitive two-pore-domain potassium (KBritish journal of pharmacology · 2018Article
- Selective and state-dependent activation of TRESK (KBritish journal of pharmacology · 2017Article
- Phosphatidylinositol (4,5)-bisphosphate dynamically regulates the KScientific reports · 2017Article
- Selective Small Molecule Activators of TREK-2 Channels Stimulate Dorsal Root Ganglion c-Fiber Nociceptor Two-Pore-Domain Potassium Channel Currents and Limit Calcium Influx.ACS chemical neuroscience · 2017Article
- Effects of analgesics and antidepressants on TREK-2 and TRESK currents.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2016Article
- Aristolochic acid, a plant extract used in the treatment of pain and linked to Balkan endemic nephropathy, is a regulator of K2P channels.British journal of pharmacology · 2016Article
- Dominant-Negative Effect of a Missense Variant in the TASK-2 (KCNK5) K+ Channel Associated with Balkan Endemic Nephropathy.PloS one · 2016Article
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2 authors at 2 institutions in 1 country.
Funding
Abstract
background and purposeAristolochic acid (AristA) is found in plants used in traditional medicines to treat pain. We investigated the action of AristA on TREK and TRESK, potassium (K2P) channels, which are potential therapeutic targets in pain. Balkan endemic nephropathy (BEN) is a renal disease associated with AristA consumption. A mutation of TASK-2 (K2P 5.1) channels (T108P) is seen in some patients susceptible to BEN, so we investigated how both this mutation and AristA affected TASK-2 channels. EXPERIMENTAL APPROACH: Currents through wild-type and mutated human K2P channels expressed in tsA201 cells were measured using whole-cell patch-clamp recordings in the presence and absence of AristA. KEY
resultsTREK-1- and TREK-2-mediated currents were enhanced by AristA (100 μM), whereas TRESK was inhibited. Inhibition of TRESK did not depend on the phosphorylation of key intracellular serines but was completely blocked by mutation of bulky residues in the inner pore (F145A_F352A). The TASK-2_T108P mutation markedly reduced both current density and ion selectivity. A related mutation (T108C) had similar but less marked effects. External alkalization and application of flufenamic acid enhanced TASK-2 and TASK-2_T108C current but did not affect TASK-2_T108P current. AristA (300 μM) produced a modest enhancement of TASK-2 current. CONCLUSIONS AND IMPLICATIONS: Enhancement of TREK-1 and TREK-2 and inhibition of TRESK by AristA may contribute to therapeutically useful effects of this compound in pain. Whilst AristA is unlikely to interact directly with TASK-2 channels in BEN, loss of functional TASK-2 channels may indirectly increase susceptibility to AristA toxicity.
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