Document Detail


Cloning, expression, and pharmacological characterization of the GPR120 free fatty acid receptor from cynomolgus monkey: comparison with human GPR120 splice variants.
MedLine Citation:
PMID:  19723586     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Activation of the GPCR GPR120 by free fatty acids has been reported to cause GLP-1 release in rodent intestine. One genetic sequence was reported for rodents, while two sequences were reported for human GPR120, BC101175 and NM_181745. A 1086 base pair sequence cloned from cynomolgus monkey colon cDNA has 85.1% and 83.4% homology with the mouse and rat GPR120 sequences, and 97.5% homology with the human BC101175 sequence. No splice variants of the cynomolgus monkey GPR120 receptor were found. Eight non-synonymous cSNPs were discovered with frequencies less than 4% in monkey samples tested. Real-time PCR demonstrated that, like the human, the highest GPR120 expression in cynomolgus monkey is in lung and colon. Studies measuring intracellular calcium release produced by free fatty acids and the small molecule GPR120 agonist GW9508 in cells expressing the cynomolgus monkey GPR120 receptor were compared to those expressing the human BC101175 splice variant. Long-chain free fatty acids produced the greatest response in cynomolgus monkey GPR120-expressing cells. GW9508 had similar efficacy at the cynomolgus monkey and at the BC101175 human GPR120 receptors. The cynomolgus monkey and the human GPR120 (BC101175) receptors have similar sequences and pharmacology. The possible significance of the alternate splice variant in human is discussed.
Authors:
Kristina Moore; Qing Zhang; Nick Murgolo; Tom Hosted; Ruth Duffy
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2009-08-31
Journal Detail:
Title:  Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology     Volume:  154     ISSN:  1879-1107     ISO Abbreviation:  Comp. Biochem. Physiol. B, Biochem. Mol. Biol.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-10-12     Completed Date:  2010-01-22     Revised Date:  2011-11-03    
Medline Journal Info:
Nlm Unique ID:  9516061     Medline TA:  Comp Biochem Physiol B Biochem Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  419-26     Citation Subset:  IM    
Affiliation:
Dept. of Cardiovascular/Metabolic Disease, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/NM181745
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MeSH Terms
Descriptor/Qualifier:
Alternative Splicing / genetics
Amino Acid Sequence
Animals
Base Sequence
Calcium / metabolism
Cell Line
Cloning, Molecular
Fatty Acids / pharmacology
Gene Expression Regulation*
Humans
Intracellular Space / drug effects,  metabolism
Macaca fascicularis*
Methylamines / pharmacology
Mice
Molecular Sequence Data
Polymerase Chain Reaction
Propionic Acids / pharmacology
Protein Isoforms / agonists,  chemistry,  genetics,  metabolism
Rats
Receptors, G-Protein-Coupled / agonists,  chemistry,  genetics*,  metabolism*
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/GW9508; 0/Methylamines; 0/O3FAR1 protein, human; 0/Propionic Acids; 0/Protein Isoforms; 0/Receptors, G-Protein-Coupled; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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