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Jordan University of Science and Technology
Stimulation of synthesis and release of brain-derived neurotropic factor from intestinal
smooth muscle cells by substance P and pituitary adenylate cyclase-activating peptide
Authors:
M Al?Qudah, R Alkahtani, HI Akbarali, KS Murthy, JR Grider
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. Key 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 & Inferences 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.