{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:16:01Z","timestamp":1790853361221,"version":"4.1.0"},"reference-count":55,"publisher":"The Endocrine Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Oxytocin plays an important role in the progression, timing, and modulation of uterine contraction during labor and is widely used as an uterotonic agent. We investigated the mechanisms regulating oxytocin receptor (OTR) signaling in human primary myometrial smooth muscle cells and the ULTR cell-line. Oxytocin produced concentration-dependent increases in both total [3H]inositol phosphate accumulation and intracellular Ca2+ concentration ([Ca2+]i); however, responses were greater and more reproducible in the ULTR cell line. Assessment of phospholipase C activity in single cells revealed that the OTR desensitizes rapidly (within 5 min) in the presence of oxytocin (100 nm). To characterize OTR desensitization further, cells were stimulated with a maximally effective concentration of oxytocin (100 nm, 30 sec) followed by a variable washout period and a second identical application of oxytocin. This brief exposure to oxytocin caused a marked decrease (&amp;gt;70%) in OTR responsiveness to rechallenge and was fully reversed by increasing the time period between agonist challenges. To assess involvement of G protein-coupled receptor kinases (GRKs) in OTR desensitization, cells were transfected with small interfering RNAs to cause specific \u226575% knockdown of GRKs 2, 3, 5, or 6. In both primary myometrial and ULTR cells, knockdown of GRK6 largely prevented oxytocin-induced OTR desensitization; in contrast, selective depletion of GRKs 2, 3, or 5 was without effect. These data indicate that GRK6 recruitment is a cardinal effector of OTR responsiveness and provide mechanistic insight into the likely in vivo regulation of OTR signaling in uterine smooth muscle.<\/jats:p>","DOI":"10.1210\/me.2009-0047","type":"journal-article","created":{"date-parts":[[2009,5,7]],"date-time":"2009-05-07T20:44:50Z","timestamp":1241729090000},"page":"1272-1280","source":"Crossref","is-referenced-by-count":40,"title":["Regulation of Oxytocin Receptor Responsiveness by G Protein-Coupled Receptor Kinase 6 in Human Myometrial Smooth Muscle"],"prefix":"10.1210","volume":"23","author":[{"given":"Jonathon M.","family":"Willets","sequence":"first","affiliation":[{"name":"Reproductive Sciences Section (J.M.W., P.J.B., G.E.M., J.C.K.), Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester Royal Infirmary, Leicester, LE2 7LX, United Kingdom"},{"name":"Department of Cell Physiology and Pharmacology (J.M.W., R.M, R.A.J.C.), University of Leicester, Leicester LE1 9HN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Brighton","sequence":"additional","affiliation":[{"name":"Reproductive Sciences Section (J.M.W., P.J.B., G.E.M., J.C.K.), Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester Royal Infirmary, Leicester, LE2 7LX, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendra","family":"Mistry","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Pharmacology (J.M.W., R.M, R.A.J.C.), University of Leicester, Leicester LE1 9HN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin E.","family":"Morris","sequence":"additional","affiliation":[{"name":"Reproductive Sciences Section (J.M.W., P.J.B., G.E.M., J.C.K.), Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester Royal Infirmary, Leicester, LE2 7LX, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin C.","family":"Konje","sequence":"additional","affiliation":[{"name":"Reproductive Sciences Section (J.M.W., P.J.B., G.E.M., J.C.K.), Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester Royal Infirmary, Leicester, LE2 7LX, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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