{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:22:17Z","timestamp":1792131737826,"version":"4.4.0"},"reference-count":58,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T00:00:00Z","timestamp":1574294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The G\u2010protein\u2010coupled receptor GPR132, also known as G2A, is activated by 9\u2010hydroxyoctadecadienoic acid (9\u2010HODE) and other oxidized fatty acids. Other suggested GPR132 agonists including lysophosphatidylcholine (LPC) have not been readily reproduced. Here, we identify\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acylamides in particular\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acylglycines, as lipid activators of GPR132 with comparable activity to 9\u2010HODE. The order\u2010of\u2010potency is\n                    <jats:italic>N<\/jats:italic>\n                    \u2010palmitoylglycine\u00a0&gt;\u00a09\u2010HODE \u2248\n                    <jats:italic>N<\/jats:italic>\n                    \u2010linoleoylglycine\u00a0&gt;\u00a0linoleamide\u00a0&gt;\u00a0N\u2010oleoylglycine \u2248\n                    <jats:italic>N<\/jats:italic>\n                    \u2010stereoylglycine\u00a0&gt;\u00a0\n                    <jats:italic>N<\/jats:italic>\n                    \u2010arachidonoylglycine\u00a0&gt;\u00a0\n                    <jats:italic>N<\/jats:italic>\n                    \u2010docosehexanoylglycine. Physiological concentrations of\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acylglycines in tissue are sufficient to activate GPR132.\n                    <jats:italic>N<\/jats:italic>\n                    \u2010linoleoylglycine and 9\u2010HODE also activate rat and mouse GPR132, despite limited sequence conservation to human. We describe pharmacological tools for GPR132, identified through drug screening. SKF\u201095667 is a novel GPR132 agonist. SB\u2010583831 and SB\u2010583355 are peptidomimetic molecules containing core amino acids (glycine and phenylalanine, respectively), and structurally related to previously described ligands. A telmisartan analog, GSK1820795A, antagonizes the actions of\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acylamides at GPR132. The synthetic cannabinoid CP\u201055\u00a0940 also activates GPR132. Molecular docking to a homology model suggested a site for lipid binding, predicting the acyl side\u2010chain to extend into the membrane bilayer between TM4 and TM5 of GPR132. Small\u2010molecule ligands are envisaged to occupy a \u201cclassical\u201d site encapsulated in the 7TM bundle. Structure\u2010directed mutagenesis indicates a critical role for arginine at position 203 in transmembrane domain 5 to mediate GPR132 activation by\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acylamides. Our data suggest distinct modes of binding for small\u2010molecule and lipid agonists to the GPR132 receptor. Antagonists, such as those described here, will be vital to understand the physiological role of this long\u2010studied target.\n                  <\/jats:p>","DOI":"10.1002\/prp2.542","type":"journal-article","created":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T06:41:51Z","timestamp":1574318511000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["<i>N<\/i>\n                    \u2010Palmitoylglycine and other\n                    <i>N<\/i>\n                    \u2010acylamides activate the lipid receptor G2A\/GPR132"],"prefix":"10.1002","volume":"7","author":[{"given":"James R.","family":"Foster","sequence":"first","affiliation":[{"name":"GlaxoSmithKline R&amp;D Ltd, Medicines Research Centre Stevenage UK"},{"name":"School of Medicine Ninewells Hospital and Medical School Dundee University Dundee 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