Mercaptoacetate and fatty acids exert direct and antagonistic effects on nodose neurons via GPR40 fatty acid receptors

Rebecca A Darling; Huan Zhao; Dallas Kinch; Ai-Jun Li; Steven M Simasko; Sue Ritter

doi:10.1152/ajpregu.00536.2013

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Mercaptoacetate and fatty acids exert direct and antagonistic effects on nodose neurons via GPR40 fatty acid receptors

Journal article

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Mercaptoacetate and fatty acids exert direct and antagonistic effects on nodose neurons via GPR40 fatty acid receptors

Rebecca A Darling, Huan Zhao, Dallas Kinch, Ai-Jun Li, Steven M Simasko and Sue Ritter

American journal of physiology. Regulatory, integrative and comparative physiology, Vol.307(1), pp.R35-R43

07/01/2014

DOI: https://doi.org/10.1152/ajpregu.00536.2013

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https://hdl.handle.net/2376/106235

PMCID: PMC4152161

PMID: 24760994

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https://doi.org/10.1152/ajpregu.00536.2013View

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Abstract

Receptors, G-Protein-Coupled - metabolism

Calcium - metabolism

Cells, Cultured

Rats

Male

Caprylates - pharmacology

Nodose Ganglion - cytology

Nodose Ganglion - metabolism

Rats, Sprague-Dawley

Dose-Response Relationship, Drug

Eating - drug effects

Animals

Sensory Receptor Cells - drug effects

Thioglycolates - pharmacology

Time Factors

Calcium Signaling - drug effects

Nodose Ganglion - drug effects

Receptors, G-Protein-Coupled - genetics

Sensory Receptor Cells - metabolism

Linoleic Acid - pharmacology

Receptors, G-Protein-Coupled - drug effects

Fatty Acids - pharmacology

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.

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Title: Mercaptoacetate and fatty acids exert direct and antagonistic effects on nodose neurons via GPR40 fatty acid receptors
Creators: Rebecca A Darling - Program in Neuroscience, Washington State University, Pullman, Washington
Huan Zhao - Program in Neuroscience, Washington State University, Pullman, Washington
Dallas Kinch - Program in Neuroscience, Washington State University, Pullman, Washington
Ai-Jun Li - Program in Neuroscience, Washington State University, Pullman, Washington
Steven M Simasko - Program in Neuroscience, Washington State University, Pullman, Washington
Sue Ritter - Program in Neuroscience, Washington State University, Pullman, Washington sjr@vetmed.wsu.edu
Publication Details: American journal of physiology. Regulatory, integrative and comparative physiology, Vol.307(1), pp.R35-R43
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: United States
Grant note: DK-067146 / NIDDK NIH HHS DK-081546 / NIDDK NIH HHS DK-040498 / NIDDK NIH HHS R01 DK097437 / NIDDK NIH HHS DK-097437 / NIDDK NIH HHS R01 DK040498 / NIDDK NIH HHS
Identifiers: 99900546743301842
Language: English
Resource Type: Journal article