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Because obesity is associated with changes in receptor signaling in many animal models, we also explored the influence of this clinical risk factor.<\/jats:p><jats:p><jats:italic>Methods<\/jats:italic>Primary cultures of human EC were exposed to \u03b1-thrombin for 16 hours, and immunologically detectable G\u03b1<jats:sub>i3<\/jats:sub>and G\u03b1<jats:sub>s<\/jats:sub>levels were measured.<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>\u03b1-Thrombin (100 nmol\/L) increased G\u03b1<jats:sub>i3<\/jats:sub>levels in EC derived from the cerebral microvasculature and superficial temporal artery (4.2\u00b11.2-fold and 2.8\u00b10.32-fold, respectively) but had no significant effect on EC derived from omental artery (<jats:italic>P<\/jats:italic>&gt;.6) or from the superficial temporal artery of obese (body mass index \u226528 kg\/m<jats:sup>2<\/jats:sup>) patients (<jats:italic>P<\/jats:italic>&gt;.4). The expression of G\u03b1<jats:sub>s<\/jats:sub>was unchanged in all cell types (<jats:italic>P<\/jats:italic>\u2265.1). Two other circulating peptides, vasoactive intestinal peptide and endothelin-1, failed to alter the expression of either G protein in EC from the cerebral microvasculature, further demonstrating the specificity of the \u03b1-thrombin effect. However, thrombin receptor activating protein-14 mimicked the \u03b1-thrombin response and increased G\u03b1<jats:sub>i3<\/jats:sub>in EC derived from the cerebral microvasculature and superficial temporal artery.<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>We conclude that \u03b1-thrombin increases G\u03b1<jats:sub>i3<\/jats:sub>expression in some EC through activation of its tethered liganded receptor. Obesity appears to suppress this action of \u03b1-thrombin.<\/jats:p>","DOI":"10.1161\/01.str.27.12.2211","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T20:10:52Z","timestamp":1308341452000},"page":"2211-2215","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["\u03b1-Thrombin Upregulates G\u03b1<sub>i3<\/sub>in Human Vascular Endothelial Cells"],"prefix":"10.1161","volume":"27","author":[{"given":"S. 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