Brain-derived neurotrophic factor enhances the contraction of intestinal muscle strips induced by SP and CGRP in mice

Background and aims: Brain-derived neurotrophic factor (BDNF) has been found in the intestinal tract of a variety of species. Its effects on visceral hyperalgesia have been examined to some degree, but limited studies have focused on gut motility. The aim of the present study was to investigate the effects of BDNF on gut motility of mice. Methods: Longitudinal muscle (LM) strips were prepared from mice ileum and distal colon. The motility of gut was evaluated by the contraction of LM strips, which was recorded by a polyphisograph in vitro. Firstly, the roles of substance P (SP), calcitonin gene-related peptide (CGRP), and acetylcholine (ACh) on the contraction of LM strips were clarified. Then the exogenous BDNF was administered, and the alterations of SP/CGRP/ACh-induced contractions of the muscle strips were explored. Finally, heterozygous BDNF+/- mice and antibody of TrkB were introduced to investigate the role of endogenous BDNF on the SP/CGRP/ACh-induced gut motility. Key results: SP (10(-8)-10(-6) mol L-1), CGRP (10(-8)-10(-7) mol L-1) and ACh (10(-8)-10(-6) mol L-1) dose-dependently caused the contraction of LM strips from ileum and distal colon, while the excitatory effect of CGRP was preceded by a transient inhibition. But 10(-6) mol L-1 CGRP inhibited the contraction of LM strips. Pretreatment with exogenous BDNF (10(-8) mol L-1) remarkably enhanced the contraction of LM strips induced by SP (10(-9)-10(-7) mol L-1) and CGRP (10(-8)-10(-9) mol L-1). However, exogenous BDNF couldn't affect the contraction induced by ACh (10(-9)-10(-7) mol L-1). The excitatory effects of Sr (10(-8)-10(-6) mol L-1) and CGRP (10(-8)-10(-7) mol L-1) on the contractions of LM strips from ileum and distal colon were significantly attenuated in BDNF+/- mice compared with those in BDNF+/+ mice, while no difference of the effects of ACh (10(-8)-10(-6) mol L-1) on LM strips was observed between BDNF+/- mice and BDNF+/+ mice. The monoclonal antibody of TrkB (TrkB-Ab) dramatically attenuated the excitatory effects of SP and CGRP on the contractions of LM strips, without affecting the excitatory effects of ACh. Conclusions and inferences: These data clarified the excitatory effects of SP. ACh and bilateral effects of CGRP on gut motility of mice and confirmed an essential role of BDNF on accelerating gut motility by enhancing the excitatory effects of SP/CGRP. (C) 2012 Elsevier B.V. All rights reserved.