PMID- 24356881 OWN - NLM STAT- MEDLINE DCOM- 20140410 LR - 20211021 IS - 1522-1547 (Electronic) IS - 0193-1857 (Print) IS - 0193-1857 (Linking) VI - 306 IP - 4 DP - 2014 Feb 15 TI - Brain-derived neurotrophic factor enhances cholinergic contraction of longitudinal muscle of rabbit intestine via activation of phospholipase C. PG - G328-37 LID - 10.1152/ajpgi.00203.2013 [doi] AB - 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-gamma, 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. FAU - Al-Qudah, M AU - Al-Qudah M AD - Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, Virginia; FAU - Anderson, C D AU - Anderson CD FAU - Mahavadi, S AU - Mahavadi S FAU - Bradley, Z L AU - Bradley ZL FAU - Akbarali, H I AU - Akbarali HI FAU - Murthy, K S AU - Murthy KS FAU - Grider, J R AU - Grider JR LA - eng GR - DK15564/DK/NIDDK NIH HHS/United States GR - R01 DK034153/DK/NIDDK NIH HHS/United States GR - DK34153/DK/NIDDK NIH HHS/United States GR - DK46367/DK/NIDDK NIH HHS/United States GR - R01 DK046367/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20131219 PL - United States TA - Am J Physiol Gastrointest Liver Physiol JT - American journal of physiology. Gastrointestinal and liver physiology JID - 100901227 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cholinergic Agonists) RN - 0 (Enzyme Inhibitors) RN - 33507-63-0 (Substance P) RN - 8Y164V895Y (Carbachol) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 3.1.4.- (Type C Phospholipases) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Carbachol/*pharmacology MH - Cholinergic Agonists/*pharmacology MH - Dose-Response Relationship, Drug MH - Enzyme Activation MH - Enzyme Inhibitors/pharmacology MH - Jejunum/*drug effects/enzymology MH - Muscle Contraction/*drug effects MH - Muscle, Smooth/*drug effects/enzymology MH - Phosphorylation MH - Rabbits MH - Receptor, trkB/drug effects/metabolism MH - Signal Transduction/drug effects MH - Substance P/pharmacology MH - Type C Phospholipases/antagonists & inhibitors/*metabolism PMC - PMC3920121 OTO - NOTNLM OT - Trk receptors OT - neurotrophins OT - smooth muscle contraction EDAT- 2013/12/21 06:00 MHDA- 2014/04/11 06:00 PMCR- 2015/02/15 CRDT- 2013/12/21 06:00 PHST- 2013/12/21 06:00 [entrez] PHST- 2013/12/21 06:00 [pubmed] PHST- 2014/04/11 06:00 [medline] PHST- 2015/02/15 00:00 [pmc-release] AID - ajpgi.00203.2013 [pii] AID - GI-00203-2013 [pii] AID - 10.1152/ajpgi.00203.2013 [doi] PST - ppublish SO - Am J Physiol Gastrointest Liver Physiol. 2014 Feb 15;306(4):G328-37. doi: 10.1152/ajpgi.00203.2013. Epub 2013 Dec 19.