Luteolin inhibits GABAA receptors in HEK cells and brain slices.
Modulation of the A type γ-aminobutyric acid receptors (GABAAR) is one of the major drug targets for neurological and psychological diseases. The natural flavonoid compound luteolin (2-(3,4-Dihydroxyphenyl)- 5,7-dihydroxy-4-chromenone) has been reported to have antidepressant, antinociceptive, and anxiolytic-like effects, which possibly involve the mechanisms of modulating GABA signaling. However, as yet detailed studies of the pharmacological effects of luteolin are still lacking, we investigated the effects of luteolin on recombinant and endogenous GABAAR-mediated current responses by electrophysiological approaches. Our results showed that luteolin inhibited GABA-mediated currents and slowed the activation kinetics of recombinant α1β2, α1β2γ2, α5β2, and α5β2γ2 receptors with different degrees of potency and efficacy. The modulatory effect of luteolin was likely dependent on the subunit composition of the receptor complex: the αβ receptors were more sensitive than the αβγ receptors. In hippocampal pyramidal neurons, luteolin significantly reduced the amplitude and slowed the rise time of miniature inhibitory postsynaptic currents (mIPSCs). However, GABAAR-mediated tonic currents were not significantly influenced by luteolin. These data suggested that luteolin has negative modulatory effects on both recombinant and endogenous GABAARs and inhibits phasic rather than tonic inhibition in hippocampus.
Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan.
Mei-Lin
ML
Shen
Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
Chen-Hung
CH
Wang
Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan.
Rita Yu-Tzu
RY
Chen
Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.|Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan.
Ning
N
Zhou
Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan.
Shung-Te
ST
Kao
Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.|Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan.
Dong Chuan
DC
Wu
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology*; D057809:HEK293 Cells; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D047311:Luteolin / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009433:Neural Inhibition; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D000700:Analgesics; D000928:Antidepressive Agents; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D047311:Luteolin