Brain-derived neurotrophic factor enhances cholinergic contraction of longitudinal muscle of rabbit intestine via activation of phospholipase C

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2014-02, Vol.306 (4), p.G328-G337
• Main Authors: Al-Qudah, M, Anderson, C D, Mahavadi, S, Bradley, Z L, Akbarali, H I, Murthy, K S, Grider, J R
• Format: Article
• Language: English
• Subjects: Animals; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - pharmacology; Carbachol - pharmacology; Cholinergic Agonists - pharmacology; Digestive system; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme Inhibitors - pharmacology; Jejunum - drug effects; Jejunum - enzymology; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - enzymology; Neuroregulation and Motility; Phosphorylation; Proteins; Rabbits; Receptor, trkB - drug effects; Receptor, trkB - metabolism; Signal Transduction - drug effects; Substance P - pharmacology; T cell receptors; Type C Phospholipases - antagonists & inhibitors; Type C Phospholipases - metabolism
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.00203.2013

Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of proteins best known for its role in neuronal survival, differentiation, migration, and synaptic plasticity in central and peripheral neurons. BDNF is also widely expressed in nonneuronal tissues including the gastrointestinal tract. The role of BDNF in intestinal smooth muscle contractility is not well defined. The aim of this study was to identify the role of BDNF in carbachol (CCh)- and substance P (SP)-induced contraction of intestinal longitudinal smooth muscle. BDNF, selective tropomyosin-related kinase B (TrkB) receptor agonists, and pharmacological inhibitors of signaling pathways were examined for their effects on contraction of rabbit intestinal longitudinal muscle strips induced by CCh and SP. BDNF activation of intracellular signaling pathways was examined by Western blot in homogenates of muscle strips and isolated muscle cells. One-hour preincubation with BDNF enhanced intestinal muscle contraction induced by CCh but not by SP. The selective synthetic TrkB agonists LM 22A4 and 7,8-dihydroxyflavone produced similar effects to BDNF. The Trk antagonist K-252a, a TrkB antibody but not p75NTR antibody, blocked the effect of BDNF. The enhancement of CCh-induced contraction by BDNF was blocked by the phospholipase C (PLC) antagonist U73122, but not by ERK1/2 or Akt antagonists. Direct measurement in muscle strips and isolated muscle cells showed that BDNF caused phosphorylation of TrkB receptors and PLC-γ, but not ERK1/2 or Akt. We conclude that exogenous BDNF augments the CCh-induced contraction of longitudinal muscle from rabbit intestine by activating TrkB receptors and subsequent PLC activation.