PMID- 20236244
OWN - NLM
STAT- MEDLINE
DCOM- 20100916
LR  - 20181113
IS  - 1365-2982 (Electronic)
IS  - 1350-1925 (Print)
IS  - 1350-1925 (Linking)
VI  - 22
IP  - 7
DP  - 2010 Jul
TI  - Expression and function of the bile acid receptor GpBAR1 (TGR5) in the murine 
      enteric nervous system.
PG  - 814-25, e227-8
LID - 10.1111/j.1365-2982.2010.01487.x [doi]
AB  - BACKGROUND: Bile acids (BAs) regulate cells by activating nuclear and 
      membrane-bound receptors. G protein coupled bile acid receptor 1 (GpBAR1) is a 
      membrane-bound G-protein-coupled receptor that can mediate the rapid, 
      transcription-independent actions of BAs. Although BAs have well-known actions on 
      motility and secretion, nothing is known about the localization and function of 
      GpBAR1 in the gastrointestinal tract. METHODS: We generated an antibody to the 
      C-terminus of human GpBAR1, and characterized the antibody by immunofluorescence 
      and Western blotting of HEK293-GpBAR1-GFP cells. We localized GpBAR1 
      immunoreactivity (IR) and mRNA in the mouse intestine, and determined the 
      mechanism by which BAs activate GpBAR1 to regulate intestinal motility. KEY 
      RESULTS: The GpBAR1 antibody specifically detected GpBAR1-GFP at the plasma 
      membrane of HEK293 cells, and interacted with proteins corresponding in mass to 
      the GpBAR1-GFP fusion protein. GpBAR1-IR and mRNA were detected in enteric 
      ganglia of the mouse stomach and small and large intestine, and in the muscularis 
      externa and mucosa of the small intestine. Within the myenteric plexus of the 
      intestine, GpBAR1-IR was localized to approximately 50% of all neurons and to 
      >80% of inhibitory motor neurons and descending interneurons expressing nitric 
      oxide synthase. Deoxycholic acid, a GpBAR1 agonist, caused a rapid and sustained 
      inhibition of spontaneous phasic activity of isolated segments of ileum and colon 
      by a neurogenic, cholinergic and nitrergic mechanism, and delayed 
      gastrointestinal transit. CONCLUSIONS & INFERENCES: G protein coupled bile acid 
      receptor 1 is unexpectedly expressed in enteric neurons. Bile acids activate 
      GpBAR1 on inhibitory motor neurons to release nitric oxide and suppress motility, 
      revealing a novel mechanism for the actions of BAs on intestinal motility.
FAU - Poole, D P
AU  - Poole DP
AD  - Department of Surgery, University of California, San Francisco, CA, USA.
FAU - Godfrey, C
AU  - Godfrey C
FAU - Cattaruzza, F
AU  - Cattaruzza F
FAU - Cottrell, G S
AU  - Cottrell GS
FAU - Kirkland, J G
AU  - Kirkland JG
FAU - Pelayo, J C
AU  - Pelayo JC
FAU - Bunnett, N W
AU  - Bunnett NW
FAU - Corvera, C U
AU  - Corvera CU
LA  - eng
GR  - R01 DK043207/DK/NIDDK NIH HHS/United States
GR  - DK07573/DK/NIDDK NIH HHS/United States
GR  - R01 DK057840/DK/NIDDK NIH HHS/United States
GR  - P30 DK026743/DK/NIDDK NIH HHS/United States
GR  - DK57840/DK/NIDDK NIH HHS/United States
GR  - R01 DK039957/DK/NIDDK NIH HHS/United States
GR  - R37 DK039957/DK/NIDDK NIH HHS/United States
GR  - P30 DK026743-26A1/DK/NIDDK NIH HHS/United States
GR  - DK39957/DK/NIDDK NIH HHS/United States
GR  - R56 DK043207/DK/NIDDK NIH HHS/United States
GR  - DK43207/DK/NIDDK NIH HHS/United States
GR  - DK026743/DK/NIDDK NIH HHS/United States
GR  - T32 DK007573/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20100312
PL  - England
TA  - Neurogastroenterol Motil
JT  - Neurogastroenterology and motility
JID - 9432572
RN  - 0 (Gpbar1 protein, mouse)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 63231-63-0 (RNA)
RN  - E0399OZS9N (Cyclic AMP)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line
MH  - Cyclic AMP/biosynthesis
MH  - Enteric Nervous System/*metabolism
MH  - Fluorescent Antibody Technique
MH  - Gastric Emptying
MH  - Gastrointestinal Motility
MH  - Gastrointestinal Tract/anatomy & histology/metabolism
MH  - Immunohistochemistry
MH  - Intestines/innervation
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microscopy, Confocal
MH  - Motor Neurons/physiology
MH  - Myenteric Plexus/metabolism
MH  - Nitric Oxide/physiology
MH  - RNA/biosynthesis/genetics
MH  - Receptors, G-Protein-Coupled/*biosynthesis/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC2891892
MID - NIHMS204264
COIS- Disclosures: No conflicts of interest exist.
EDAT- 2010/03/20 06:00
MHDA- 2010/09/18 06:00
PMCR- 2011/07/01
CRDT- 2010/03/19 06:00
PHST- 2010/03/19 06:00 [entrez]
PHST- 2010/03/20 06:00 [pubmed]
PHST- 2010/09/18 06:00 [medline]
PHST- 2011/07/01 00:00 [pmc-release]
AID - NMO1487 [pii]
AID - 10.1111/j.1365-2982.2010.01487.x [doi]
PST - ppublish
SO  - Neurogastroenterol Motil. 2010 Jul;22(7):814-25, e227-8. doi: 
      10.1111/j.1365-2982.2010.01487.x. Epub 2010 Mar 12.