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This Article Full Text Full Text (PDF) All Versions of this Article: 290/3/C785    most recent 00462.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Stewart, G. Articles by McLaughlin, J. T. Search for Related Content PubMed PubMed Citation Articles by Stewart, G. Articles by McLaughlin, J. T.

RECEPTORS AND SIGNAL TRANSDUCTION

Mouse GPR40 heterologously expressed in Xenopus oocytes is activated by short-, medium-, and long-chain fatty acids

¹Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom; ²Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Sapporo, Japan; and ³Gastrointestinal Sciences, Clinical Sciences Building, Hope Hospital, Salford, United Kingdom

Submitted 15 September 2005 ; accepted in final form 24 October 2005

Several orphan G protein-coupled receptors, including GPR40, have recently been shown to be responsive to fatty acids. Although previous reports have suggested GPR40 detects medium- and long-chain fatty acids, it has been reported to be unresponsive to short chain fatty acids. In this study, we have heterologously expressed mouse GPR40 in Xenopus laevis oocytes and measured fatty acid-induced increases in intracellular Ca²⁺, via two electrode voltage clamp recordings of the endogenous Ca²⁺-activated chloride conductance. Exposure to 500 µM linoleic acid (C18:2), a long-chain fatty acid, stimulated significant currents in mGPR40-injected oocytes (P < 0.01, ANOVA), but not in water-injected control oocytes (not significant, ANOVA). These currents were confirmed as Ca²⁺-activated chloride conductances because they were biphasic, sensitive to changes in external pH, and inhibited by DIDS. Similar currents were observed with medium-chain fatty acids, such as lauric acid (C12:0) (P < 0.01, ANOVA), and more importantly, with short-chain fatty acids, such as butyric acid (C4:0) (P < 0.01, ANOVA). In contrast, no responses were observed in mGPR40-injected oocytes exposed to either acetic acid (C2:0) or propionic acid (C3:0). Therefore, GPR40 has the capacity to respond to fatty acids with chain lengths of four or greater. This finding has important implications for understanding the structure:function relationship of fatty acid sensors, and potentially for short-chain fatty acid sensing in the gastrointestinal tract.

fatty acid chain length; nutrient sensing