ArticleBritish journal of pharmacology2011
Naringin directly activates inwardly rectifying potassium channels at an overlapping binding site to tertiapin-Q.
Article in British journal of pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
- An In Silico Investigation of the Pathogenic G151R G Protein-Gated Inwardly Rectifying KBiology · 2024Article
- Identification of Potential Modulators of a Pathogenic G Protein-Gated Inwardly Rectifying KMolecules (Basel, Switzerland) · 2023Article
- Flavonoids as Modulators of Potassium Channels.International journal of molecular sciences · 2023Review
- Acetylcholine regulation of GnRH neuronal activity: A circuit in the medial septum.Frontiers in endocrinology · 2023Article
- A novel small-molecule selective activator of homomeric GIRK4 channels.The Journal of biological chemistry · 2022Article
- AsKC11, a Kunitz Peptide fromMarine drugs · 2022Article
- Naringin improves sepsis-induced intestinal injury by modulating macrophage polarization via PPARγ/miR-21 axis.Molecular therapy. Nucleic acids · 2021Article
- Next-generation inward rectifier potassium channel modulators: discovery and molecular pharmacology.American journal of physiology. Cell physiology · 2021Review
- Advances in Targeting GIRK Channels in Disease.Trends in pharmacological sciences · 2021Review
- Kir Channel Molecular Physiology, Pharmacology, and Therapeutic Implications.Handbook of experimental pharmacology · 2021Review
- Hippocampal long-term synaptic depression and memory deficits induced in early amyloidopathy are prevented by enhancing G-protein-gated inwardly rectifying potassium channel activity.Journal of neurochemistry · 2020Article
- The small molecule GAT1508 activates brain-specific GIRK1/2 channel heteromers and facilitates conditioned fear extinction in rodents.The Journal of biological chemistry · 2020Article
- Article
- Ivermectin activates GIRK channels in a PIPThe Journal of physiology · 2017Article
- Optical control of neuronal activity using a light-operated GIRK channel opener (LOGO).Chemical science · 2016Article
- Ability of naringenin, a bioflavonoid, to activate M-type potassium current in motor neuron-like cells and to increase BKCa-channel activity in HEK293T cells transfected with α-hSlo subunit.BMC neuroscience · 2014Article
- Mechanisms underlying the activation of G-protein-gated inwardly rectifying K+ (GIRK) channels by the novel anxiolytic drug, ML297.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Presence of multiple binding sites on α9α10 nAChR receptors alludes to stoichiometric-dependent action of the α-conotoxin, Vc1.1.Biochemical pharmacology · 2014Article
- G protein-gated inwardly rectifying potassium (KIR3) channels play a primary role in the antinociceptive effect of oxycodone, but not morphine, at supraspinal sites.British journal of pharmacology · 2014Article
- GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimer's disease.Frontiers in cellular neuroscience · 2014Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundG protein-coupled inwardly rectifying potassium (K(IR) 3) channels are important proteins that regulate numerous physiological processes including excitatory responses in the CNS and the control of heart rate. Flavonoids have been shown to have significant health benefits and are a diverse source of compounds for identifying agents with novel mechanisms of action. EXPERIMENTAL APPROACH: The flavonoid glycoside, naringin, was evaluated on recombinant human K(IR) 3.1-3.4 and K(IR) 3.1-3.2 expressed in Xenopus oocytes using two-electrode voltage clamp methods. In addition, we evaluated the activity of naringin alone and in the presence of the K(IR) 3 channel blocker tertiapin-Q (0.5 nM, 1 nM and 3 nM) at recombinant K(IR) 3.1-3.4 channels. Site-directed mutagenesis was used to identify amino acids within the M1-M2 loop of the K(IR) 3.1(F137S) mutant channel important for naringin's activity. KEY
resultsNaringin (100 µM) had minimal effect on uninjected oocytes but activated K(IR) 3.1-3.4 and K(IR) 3.1-3.2 channels. The activation by naringin of K(IR) 3.1-3.4 channels was inhibited by tertiapin-Q in a competitive manner. An alanine-scan performed on the K(IR) 3.1(F137S) mutant channel, replacing one by one aromatic amino acids within the M1-M2 loop, identified tyrosines 148 and 150 to be significantly contributing to the affinity of naringin as these mutations reduced the activity of naringin by 20- and 40-fold respectively. CONCLUSIONS AND IMPLICATIONS: These results show that naringin is a direct activator of K(IR) 3 channels and that tertiapin-Q shares an overlapping binding site on the K(IR) 3.1-3.4. This is the first example of a ligand that activates K(IR) 3 channels by binding to the extracellular M1-M2 linker of the channel.
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