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- W2089479938 endingPage "R43" @default.
- W2089479938 startingPage "R35" @default.
- W2089479938 abstract "β-mercaptoacetate (MA) is a drug known to block mitochondrial oxidation of medium- and long-chain fatty acids (FAs) and to stimulate feeding. Because MA-induced feeding is vagally dependent, it has been assumed that the feeding response is mediated by MA's antimetabolic action at a peripheral, vagally innervated site. However, MA's site of action has not yet been identified. Therefore, we used fluorescent calcium measurements in isolated neurons from rat nodose ganglia to determine whether MA has direct effects on vagal sensory neurons. We found that MA alone did not alter cytosolic calcium concentrations in nodose neurons. However, MA (60 μM to 6 mM) significantly decreased calcium responses to both linoleic acid (LA; 10 μM) and caprylic acid (C8; 10 μM) in all neurons responsive to LA and C8. GW9508 (40 μM), an agonist of the FA receptor, G protein-coupled receptor 40 (GPR40), also increased calcium levels almost exclusively in FA-responsive neurons. MA significantly inhibited this response to GW9508. MA did not inhibit calcium responses to serotonin, high K + , or capsaicin, which do not utilize GPRs, or to CCK, which acts on a different GPR. GPR40 was detected in nodose ganglia by RT-PCR. Results suggest that FAs directly activate vagal sensory neurons via GPR40 and that MA antagonizes this effect. Thus, we propose that MA's nonmetabolic actions on GPR40 membrane receptors, expressed by multiple peripheral tissues in addition to the vagus nerve, may contribute to or mediate MA-induced stimulation of feeding." @default.
- W2089479938 created "2016-06-24" @default.
- W2089479938 creator A5008730677 @default.
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- W2089479938 creator A5035177570 @default.
- W2089479938 creator A5090157480 @default.
- W2089479938 date "2014-07-01" @default.
- W2089479938 modified "2023-09-23" @default.
- W2089479938 title "Mercaptoacetate and fatty acids exert direct and antagonistic effects on nodose neurons via GPR40 fatty acid receptors" @default.
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- W2089479938 doi "https://doi.org/10.1152/ajpregu.00536.2013" @default.
- W2089479938 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4152161" @default.
- W2089479938 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24760994" @default.
- W2089479938 hasPublicationYear "2014" @default.
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