title: Stimulation of synthesis and release of brain-derived neurotropic factor from intestinal smooth muscle cells by substance P and pituitary adenylate cyclase-activating peptide.
abstract: BACKGROUND
  Brain-derived neurotrophic factor (BDNF) is a neurotrophin present in the intestine where it participates in survival and growth of enteric neurons, augmentation of enteric circuits, and stimulation of intestinal peristalsis and propulsion. Previous studies largely focused on the role of neural and mucosal BDNF. The expression and release of BDNF from intestinal smooth muscle and the interaction with enteric neuropeptides has not been studied in gut.
  
  
  METHODS
  The expression and secretion of BDNF from smooth muscle cultured from the rabbit intestinal longitudinal muscle layer in response to substance P (SP) and pituitary adenylate cyclase-activating peptide (PACAP) was measured by western blot and enzyme-linked immunosorbent assay. BDNF mRNA was measured by reverse-transcription polymerase chain reaction.
  
  
  RESULTS
  The expression of BNDF protein and mRNA was greater in smooth muscle cells (SMCs) from the longitudinal muscle than from circular muscle layer. PACAP and SP increased the expression of BDNF protein and mRNA in cultured longitudinal SMCs. PACAP and SP also stimulated the secretion of BDNF from cultured longitudinal SMCs. Chelation of intracellular calcium with BAPTA (1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) prevented SP-induced increase in BDNF mRNA and protein expression and SP-induced secretion of BDNF.
  
  
  CONCLUSIONS
  Neuropeptides known to be present in enteric neurons innervating the longitudinal layer increase the expression of BDNF mRNA and protein in SMCs and stimulate the release of BDNF. Considering the ability of BDNF to enhance smooth muscle contraction, this autocrine loop may partially explain the characteristic hypercontractility of longitudinal muscle in inflammatory bowel disease.
authors.affiliation: Department of Physiology and Biophysics, VCU Program in Enteric Neuromuscular Sciences (VPENS), School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Al-Qudah
authors.affiliation: Department of Physiology and Biophysics, VCU Program in Enteric Neuromuscular Sciences (VPENS), School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Alkahtani
authors.affiliation: Department of Pharmacology and Toxicology, VCU Program in Enteric Neuromuscular Sciences (VPENS), School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: H I
authors.initials: HI
authors.lastname: Akbarali
authors.affiliation: Department of Physiology and Biophysics, VCU Program in Enteric Neuromuscular Sciences (VPENS), School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Murthy
authors.affiliation: Department of Physiology and Biophysics, VCU Program in Enteric Neuromuscular Sciences (VPENS), School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Grider
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D020013:Calcium Signaling; D007422:Intestines / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D011817:Rabbits; D013373:Substance P / Q000494:pharmacology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D013373:Substance P
keywords: gastrointestinal tract; gut smooth muscle; motility; neuropeptides; neurotrophins; tachykinins