{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T19:45:25Z","timestamp":1767815125840,"version":"3.49.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2008,1,1]],"date-time":"2008-01-01T00:00:00Z","timestamp":1199145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["rep.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In the present study, we studied the potential regulation by rat myometrial \u03b11-adrenergic receptors (\u03b11-AR) of the newly identified Gh\u03b1 protein\/phospholipase C\u03b41 (PLC\u03b41) signaling pathway and compared myometrial inositol phosphates (InsP) production and activity of the uterine circular muscle in response to \u03b11-AR activation between mid-pregnancy and term. For this, we quantified the level of rat myometrial \u03b11-AR coupling to Gh\u03b1 protein by photoaffinity-labeling, the cytosolic amount of PLC\u03b41 enzyme by immunoblotting, and the expression level of \u03b11-AR subtypes by RT-PCR. The results showed an increased level of \u03b11-AR\/Gh\u03b1 protein coupling and the amount of PLC\u03b41 at term (+147 and +65% respectively, versus mid-pregnancy). This was correlated with an up-regulation of \u03b11d-AR subtype (+70% versus mid-pregnancy). Incubation of myometrial strips with phenylephrine (Phe), a global \u03b11-agonist, increased InsP production in a dose-dependent manner at both mid-pregnancy and term, but with an enhanced potency (tenfold decrease in EC50 value) at term. Phe also dose-dependently induced contraction of the circular muscle at both mid-pregnancy and term. However, unlike InsP response, no amelioration of potency was observed at term. Similar results were obtained with the endogenous agonist norepinephrine. Our results show, for the first time, that rat myometrial \u03b11d-AR\/Gh\u03b1\/PLC\u03b41 signaling pathway is up-regulated at term. This is associated with an increased potency of \u03b11-AR to elicit InsP production but not uterine contraction at this period. It is thus hypothesized that \u03b11-AR, through activation of Gh\u03b1\/PLC\u03b41 system, are not primarily involved in the initiation of labor but may rather regulate responses such as myometrial cell proliferation or hypertrophy.<\/jats:p>","DOI":"10.1530\/rep-07-0332","type":"journal-article","created":{"date-parts":[[2007,12,25]],"date-time":"2007-12-25T16:37:42Z","timestamp":1198600662000},"page":"55-62","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":12,"title":["Increased potency of \u03b11-adrenergic receptors to induce inositol phosphates production correlates with the up-regulation of \u03b11d\/Gh\u03b1\/phospholipase C\u03b41 signaling pathway in term rat myometrium"],"prefix":"10.1093","volume":"135","author":[{"given":"M","family":"Dupuis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Houdeau","sequence":"additional","affiliation":[{"name":"CNRS UMR 7079 Laboratoire de Physiologie et Physiopathologie, 75231 Paris Cedex 05, France and 1INRA UMR 1054 Unit\u00e9 de Neuro-Gastroent\u00e9rologie and Nutrition, 31931 Toulouse Cedex 09, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Mhaouty-Kodja","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,1,1]]},"reference":[{"key":"2026010713143827700_bib1","doi-asserted-by":"crossref","first-page":"5591","DOI":"10.1074\/jbc.M008252200","article-title":"Phospholipase C\u03b41 is a guanine nucleotide exchanging factor for transglutaminase II (G\u03b1h) and promotes \u03b11B-adrenoceptor-mediated GTP binding and intracellular calcium release","volume":"276","author":"Baek","year":"2001","journal-title":"Journal of Biological Chemistry"},{"key":"2026010713143827700_bib2","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Analytical Biochemistry"},{"key":"2026010713143827700_bib3","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/S0022-3565(25)20237-3","article-title":"Alpha-1 adrenergic receptor: binding and phosphoinositide breakdown in human myometrium","volume":"258","author":"Breuiller-Fouche","year":"1991","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"2026010713143827700_bib4","doi-asserted-by":"crossref","first-page":"32385","DOI":"10.1074\/jbc.271.50.32385","article-title":"\u03b11-adrenergic receptor signaling via Gh is subtype specific and independent of its transglutaminase activity","volume":"271","author":"Chen","year":"1996","journal-title":"Journal of Biological Chemistry"},{"key":"2026010713143827700_bib5","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1677\/jme.0.0060137","article-title":"Regulation by progesterone of the high-affinity state of myometrial \u03b2-adrenergic receptor and of adenylate cyclase activity in the pregnant rat","volume":"6","author":"Cohen-Tannoudji","year":"1991","journal-title":"Journal of Molecular Endocrinology"},{"key":"2026010713143827700_bib6","doi-asserted-by":"crossref","first-page":"27390","DOI":"10.1016\/S0021-9258(19)74262-8","article-title":"Evidence that the Gh protein is a signal mediator from \u03b11-adrenoceptor to a phospholipase C. II. Purification and characterization of a Gh-coupled 69-kDa phospholipase C and reconstitution of \u03b11-adrenoceptor, Gh family, and phospholipase C","volume":"268","author":"Das","year":"1993","journal-title":"Journal of Biological Chemistry"},{"key":"2026010713143827700_bib7","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1242\/jcs.02892","article-title":"Ablation of connexin43 in uterine smooth muscle cells of the mouse causes delayed parturition","volume":"119","author":"D\u00f6ring","year":"2006","journal-title":"Journal of Cell Science"},{"key":"2026010713143827700_bib8","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/mrd.10148","article-title":"Altered levels of mRNA expression and pharmacological reactivity of \u03b11-adrenergic receptor subtypes in the late-pregnant rat myometrium","volume":"62","author":"Ducza","year":"2002","journal-title":"Molecular Reproduction and Development"},{"key":"2026010713143827700_bib9","doi-asserted-by":"crossref","first-page":"19257","DOI":"10.1074\/jbc.M314299200","article-title":"Functional coupling of rat myometrial \u03b11-adrenergic receptors to Gh\u03b1\/tissue transglutaminase 2 during pregnancy","volume":"279","author":"Dupuis","year":"2004","journal-title":"Journal of Biological Chemistry"},{"key":"2026010713143827700_bib10","doi-asserted-by":"crossref","first-page":"16451","DOI":"10.1074\/jbc.271.28.16451","article-title":"Evidence that phospholipase \u03b41 is the effector in the Gh (transglutaminase II)-mediated signaling","volume":"271","author":"Feng","year":"1996","journal-title":"Journal of Biological Chemistry"},{"key":"2026010713143827700_bib11","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1677\/joe.1.06388","article-title":"Up-regulation of rat myometrial phospholipases C\u03b21 and C\u03b23 correlates with increased term sensitivity to carbachol and oxytocin","volume":"187","author":"Houdeau","year":"2005","journal-title":"Journal of Endocrinology"},{"key":"2026010713143827700_bib12","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0960-0760(03)00006-2","article-title":"Calreticulin inhibits the MEK1,2-ERK1,2 pathway in \u03b11-adrenergic receptor\/Gh-stimulated hypertrophy of neonatal rat cardiomyocytes","volume":"84","author":"Lee","year":"2003","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"2026010713143827700_bib13","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1530\/jrf.0.0760415","article-title":"Evidence for a noradrenergic transmission in the control of parturition in the rat","volume":"76","author":"Legrand","year":"1986","journal-title":"Journal of Reproduction and Fertility"},{"key":"2026010713143827700_bib14","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/S0022-3565(25)23110-X","article-title":"Selective distribution of alpha-1 and beta adrenoceptors in pregnant rat uterus visualized by autoradiography","volume":"256","author":"Legrand","year":"1991","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"2026010713143827700_bib15","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S0022-3565(25)38303-5","article-title":"Heterogeneity of alpha-2 adrenoceptors in pregnant rat uterus: identification of subtypes and autoradiographic distribution","volume":"266","author":"Legrand","year":"1993","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"2026010713143827700_bib16","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1095\/biolreprod57.5.1175","article-title":"The alpha1B-adrenergic receptor subtype activates the phospholipase C signaling pathway in rat myometrium at parturition","volume":"57","author":"Limon-Boulez","year":"1997","journal-title":"Biology of Reproduction"},{"key":"2026010713143827700_bib17","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1677\/joe.0.0670371","article-title":"Effects of injections of monoamine oxidase inhibitor or saline into the uterus in late pregnancy on uterine catecholamine levels related to abnormal parturition in rats","volume":"67","author":"Maltier","year":"1975","journal-title":"Journal of Endocrinology"},{"key":"2026010713143827700_bib18","doi-asserted-by":"crossref","first-page":"11012","DOI":"10.1074\/jbc.270.18.11012","article-title":"Characteristics of the \u03b12-\/\u03b22-adrenergic receptor-coupled adenylyl cyclase system in rat myometrium during pregnancy","volume":"270","author":"Mhaouty","year":"1995","journal-title":"Journal of Biological Chemistry"},{"key":"2026010713143827700_bib19","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/j.1469-7793.2001.00123.x","article-title":"Catecholamines are not linked to myometrial phospholipase C and uterine contraction in late pregnant and parturient mouse","volume":"536","author":"Mhaouty-Kodja","year":"2001","journal-title":"Journal of Physiology"},{"key":"2026010713143827700_bib20","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1095\/biolreprod.103.021535","article-title":"Regulation of myometrial phospholipase C system and uterine contraction by \u03b2-adrenergic receptors in mid-pregnant rat","volume":"70","author":"Mhaouty-Kodja","year":"2004","journal-title":"Biology of Reproduction"},{"key":"2026010713143827700_bib21","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1046\/j.1440-1681.2003.03811.x","article-title":"Synergism between \u03b22-adrenoceptor agonists and subtype-selective \u03b11A-adrenoceptor antagonists in the tocolytic effect on pregnant rat uterus in vitro","volume":"30","author":"Mihalyi","year":"2003","journal-title":"Clinical and Experimental Pharmacology and Physiology"},{"key":"2026010713143827700_bib22","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1126\/science.7911253","article-title":"Gh: a GTP-binding protein with transglutaminase activity and receptor signaling function","volume":"264","author":"Nakaoka","year":"1994","journal-title":"Science"},{"key":"2026010713143827700_bib23","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/biolreprod\/3.1.13","article-title":"Uterine response to adrenergic nerve stimulation in the guinea pig","volume":"3","author":"Russe","year":"1970","journal-title":"Biology of Reproduction"},{"key":"2026010713143827700_bib24","doi-asserted-by":"crossref","first-page":"22213","DOI":"10.1074\/jbc.M000091200","article-title":"Roles of tissue transglutaminase in ethanol-induced inhibition of hepatocyte proliferation and \u03b11-adrenergic signal transduction","volume":"275","author":"Wu","year":"2000","journal-title":"Journal of Biological Chemistry"},{"key":"2026010713143827700_bib25","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.bbalip.2006.02.016","article-title":"Coordinated intracellular translocation of phosphoinositide-specific phospholipase C-\u03b4 with the cell cycle","volume":"1761","author":"Yagisawa","year":"2006","journal-title":"Biochimica et Biophysica Acta"},{"key":"2026010713143827700_bib26","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1161\/01.RES.0000071749.22027.45","article-title":"COX-2-dependent cardiac failure in Gh\/tTG transgenic mice","volume":"92","author":"Zhang","year":"2003","journal-title":"Circulation Research"}],"container-title":["REPRODUCTION"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rep.bioscientifica.com\/view\/journals\/rep\/135\/1\/55.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/reproduction\/article-pdf\/135\/1\/55\/64611200\/55.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/reproduction\/article-pdf\/135\/1\/55\/64611200\/55.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T18:28:41Z","timestamp":1767810521000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/reproduction\/article\/135\/1\/55\/8252752"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,1]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,1,1]]}},"URL":"https:\/\/doi.org\/10.1530\/rep-07-0332","relation":{},"ISSN":["1470-1626","1741-7899"],"issn-type":[{"value":"1470-1626","type":"print"},{"value":"1741-7899","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2008,1,1]]},"published":{"date-parts":[[2008,1,1]]}}}