The novel TrkB receptor agonist 7,8-dihydroxyflavone enhances neuromuscular transmission
Carlos B Mantilla1, Leonid G Ermilov
1Department of Anesthesiology, College of Medicine, Mayo Clinic, 200 First Street SW, Joseph 4W-184F, Rochester, Minnesota 55905, USA. mantilla.carlos@mayo.edu
Abstract:
Neurotrophin signaling at the neuromuscular junction modulates cholinergic transmission and enhances neuromuscular transmission via the tropomyosin-related kinase receptor subtype B (TrkB).A novel flavonoid, 7,8-dihydroxyflavone (7,8-DHF), selectively activates TrkB receptors. Using TrkB(F616A) mice that are susceptible to specific inhibition of TrkB activity by 1NMPP1, we show that neuromuscular transmission is enhanced by 7,8-DHF (∽32%) via activation of TrkB in diaphragm muscle. The small molecule 7,8-DHF may constitute a novel therapy to improve neuromuscular function.
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