{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:56:19Z","timestamp":1790060179623,"version":"4.0.1"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,8,2]]},"abstract":"<jats:sec xml:lang=\"en\"><jats:title>Background<\/jats:title><jats:p xml:lang=\"en\">Recently, we provided evidence that \u03b1<jats:sub>1<\/jats:sub>\u2010adrenergic receptors (<jats:styled-content style=\"fixed-case\">ARs<\/jats:styled-content>) in vascular smooth muscle are regulated by chemokine (C\u2010X\u2010C motif) receptor (<jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>) 4 and atypical chemokine receptor 3 (<jats:styled-content style=\"fixed-case\">ACKR<\/jats:styled-content>3). While we showed that<jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4 controls \u03b1<jats:sub>1<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">ARs<\/jats:styled-content>through formation of heteromeric receptor complexes in human vascular smooth muscle cells (<jats:styled-content style=\"fixed-case\">hVSMCs<\/jats:styled-content>), the molecular basis underlying cross\u2010talk between<jats:styled-content style=\"fixed-case\">ACKR<\/jats:styled-content>3 and \u03b1<jats:sub>1<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">ARs<\/jats:styled-content>is unknown.<\/jats:p><\/jats:sec><jats:sec xml:lang=\"en\"><jats:title>Methods and Results<\/jats:title><jats:p xml:lang=\"en\">We show that<jats:styled-content style=\"fixed-case\">ACKR<\/jats:styled-content>3 agonists inhibit inositol trisphosphate production in<jats:styled-content style=\"fixed-case\">hVSMCs<\/jats:styled-content>on stimulation with phenylephrine. In proximity ligation assays and co\u2010immunoprecipitation experiments, we observed that recombinant and endogenous<jats:styled-content style=\"fixed-case\">ACKR<\/jats:styled-content>3 form heteromeric complexes with \u03b1<jats:sub>1A\/B\/D<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>. While small interfering RNA knockdown of<jats:styled-content style=\"fixed-case\">ACKR<\/jats:styled-content>3 in<jats:styled-content style=\"fixed-case\">hVSMCs<\/jats:styled-content>reduced \u03b1<jats:sub>1B\/D<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>:<jats:styled-content style=\"fixed-case\">ACKR<\/jats:styled-content>3,<jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4:<jats:styled-content style=\"fixed-case\">ACKR<\/jats:styled-content>3, and \u03b1<jats:sub>1B\/D<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>:<jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4 complexes, small interfering RNA knockdown of<jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4 reduced \u03b1<jats:sub>1B\/D<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>:<jats:styled-content style=\"fixed-case\">ACKR<\/jats:styled-content>3 heteromers. Phenylephrine\u2010induced inositol trisphosphate production from<jats:styled-content style=\"fixed-case\">hVSMCs<\/jats:styled-content>was abolished after<jats:styled-content style=\"fixed-case\">ACKR<\/jats:styled-content>3 and<jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4 small interfering RNA knockdown. Peptide analogs of transmembrane domains 2\/4\/7 of<jats:styled-content style=\"fixed-case\">ACKR<\/jats:styled-content>3 showed differential effects on heteromerization between<jats:styled-content style=\"fixed-case\">ACKR<\/jats:styled-content>3, \u03b1<jats:sub>1A\/B\/D<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">AR,<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4. While the transmembrane domain 2 peptide interfered with \u03b1<jats:sub>1B\/D<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>:<jats:styled-content style=\"fixed-case\">ACKR<\/jats:styled-content>3 and<jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4:<jats:styled-content style=\"fixed-case\">ACKR<\/jats:styled-content>3 heteromerization, it increased heteromerization between<jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4 and \u03b1<jats:sub>1A\/B<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>. The transmembrane domain 2 peptide inhibited<jats:styled-content style=\"fixed-case\">ACKR<\/jats:styled-content>3 but did not affect \u03b1<jats:sub>1b<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>in \u03b2\u2010arrestin recruitment assays. Furthermore, the transmembrane domain 2 peptide inhibited phenylephrine\u2010induced inositol trisphosphate production in hVSMCs and attenuated phenylephrine\u2010induced constriction of mesenteric arteries.<\/jats:p><\/jats:sec><jats:sec xml:lang=\"en\"><jats:title>Conclusions<\/jats:title><jats:p xml:lang=\"en\">\u03b1<jats:sub>1<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">ARs<\/jats:styled-content>form hetero\u2010oligomeric complexes with the<jats:styled-content style=\"fixed-case\">ACKR<\/jats:styled-content>3:<jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4 heteromer, which is required for \u03b1<jats:sub>1B\/D<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>function, and activation of<jats:styled-content style=\"fixed-case\">ACKR<\/jats:styled-content>3 negatively regulates \u03b1<jats:sub>1<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>s. G protein\u2013coupled receptor hetero\u2010oligomerization is a dynamic process, which depends on the relative abundance of available receptor partners. Endogenous \u03b1<jats:sub>1<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>s function within a network of hetero\u2010oligomeric receptor complexes.<\/jats:p><\/jats:sec>","DOI":"10.1161\/jaha.117.006575","type":"journal-article","created":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T18:25:38Z","timestamp":1504290338000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["\u03b1<sub>1<\/sub>\u2010Adrenergic Receptors Function Within Hetero\u2010Oligomeric Complexes With Atypical Chemokine Receptor 3 and Chemokine (C\u2010X\u2010C motif) Receptor 4 in Vascular Smooth Muscle Cells"],"prefix":"10.1161","volume":"6","author":[{"given":"Lauren J.","family":"Albee","sequence":"first","affiliation":[{"name":"Department of Surgery, Burn and Shock Trauma Research Institute, Loyola University Chicago Stritch School of Medicine, Maywood, 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