title: G protein-coupled estrogen receptor is involved in modulating colonic motor function via nitric oxide release in C57BL/6 female mice.
abstract: BACKGROUND
  Estrogen may regulate gastrointestinal motor functions, but the mechanism(s) is not totally understood. Here, we investigated whether G protein-coupled estrogen receptor (GPER/GPR30) was involved in regulating colonic motor functions and explored the underlying physiological mechanisms.
  
  
  METHODS
  Adult female C57BL/6 mice were used. The expression and localization of GPER were examined by RT-PCR, western blot, and immuno-labeling. The role of GPER in modulating colonic motor functions was assessed by the bead propulsion test in vivo and organ bath experiments in vitro.
  
  
  RESULTS
  GPER was expressed in colonic myenteric neurons. The colonic transit time (CTT) in proestrus and estrus was significantly longer than that in diestrus. In vivo treatment with the selective GPER blocker G15 significantly shortened CTT in proestrus and estrus. In ovariectomized mice, acute estrogen supplementation increased CTT, which could be abolished by G15 co-administration. The GPER agonist G-1 caused a concentration-dependent inhibition of carbachol -induced circular muscle strips contraction, which was abolished by tetrodotoxin and the neuronal nitric oxide synthase (nNOS) inhibitor N-propyl-l-arginine. G-1 stimulated NO production in isolated longitudinal muscle myenteric plexus and cultured myenteric neurons, which was dependent on nNOS. Immunofluorescence labeling showed co-localization of GPER with nNOS in the myenteric plexus.
  
  
  CONCLUSIONS
  We suggest that activation of GPER exerts an inhibitory effect on colonic motility by promoting NO release from myenteric nitrergic nerves. These results raise a possibility that GPER may be involved in mediating the inhibitory effect of estrogen on colonic motor functions, via a non-genomic, neurogenic mechanism.
authors.affiliation: Department of Pathophysiology, Medical School, Shandong University, Jinan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Medical School, Shandong University, Jinan, China.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, Medical School, Shandong University, Jinan, China.
authors.forename: F
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Department of Pathophysiology, Medical School, Shandong University, Jinan, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Physiology, Medical School, Shandong University, Jinan, China.
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Medical School, Shandong University, Jinan, China.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Medical School, Shandong University, Jinan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Pathophysiology, Medical School, Shandong University, Jinan, China.
authors.forename: R
authors.initials: R
authors.lastname: Lu
authors.affiliation: Department of Pathophysiology, Medical School, Shandong University, Jinan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Department of Pathophysiology, Medical School, Shandong University, Jinan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Medical School, Shandong University, Jinan, China.
authors.forename: B
authors.initials: B
authors.lastname: Xue
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003106:Colon / Q000502:physiology*; D005260:Female; D005769:Gastrointestinal Motility / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009197:Myenteric Plexus / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009924:Organ Culture Techniques; D010052:Ovariectomy; D011960:Receptors, Estrogen / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C532507:GPER1 protein, mouse; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D009569:Nitric Oxide
keywords: G protein-coupled estrogen receptor; colon; motor function; myenteric neuron; nitric oxide