{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:15:32Z","timestamp":1760148932636,"version":"build-2065373602"},"reference-count":97,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,17]],"date-time":"2023-06-17T00:00:00Z","timestamp":1686960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Eunice Kennedy Shriver National Institute for Child Health and Human Development to ILO","award":["HD091114","HD108728"],"award-info":[{"award-number":["HD091114","HD108728"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Preterm labor leading to preterm birth is the leading cause of infant morbidity and mortality. At the present time, nothing can reliably halt labor once it begins. The knowledge that agonists of the \u03b22 adrenergic receptor relax airway smooth muscle and are effective in the treatment of asthma led to the notion that \u03b22 mimetics would prevent preterm birth by relaxing uterine smooth muscle. The activation of cAMP-dependent protein kinase by \u03b22 receptors is unable to provide meaningful tocolysis. The failure of \u03b22 agonists such as ritodrine and terbutaline to prevent preterm birth suggests that the regulation of uterine smooth muscle is disparate from that of airway. Other smooth muscle quiescent-mediating molecules, such as nitric oxide, relax vascular smooth muscle in a cGMP-protein kinase G-dependent manner; however, nitric oxide activation of protein kinase G fails to explain the relaxation of the myometrium to nitric oxide. Moreover, nitric oxide-mediated relaxation is blunted in preterm labor, and thus, for this reason and because of the fall in maternal blood pressure, nitric oxide cannot be employed as a tocolytic. The \u03b23 adrenergic receptor-mediated relaxation of the human myometrium is claimed to be cAMP-dependent protein kinase-dependent. This is scientifically displeasing given the failure of \u03b22 agonists as tocolytics and suggests a non-canonical signaling role for \u03b23AR in myometrium. The addition of the \u03b23 agonist mirabegron to pregnant human myometrial strips in the tissue bath relaxes oxytocin-induced contractions. Mirabegron stimulates nitric oxide production in myometrial microvascular endothelial cells, and the relaxation of uterine tissue in vitro is partially blocked by the addition of the endothelial nitric oxide synthase blocker N\u03c9-Nitro-L-arginine. Recent data suggest that both endothelial and smooth muscle cells respond to \u03b23 stimulation and contribute to relaxation through disparate signaling pathways. The repurposing of approved medications such as mirabegron (Mybetriq\u2122) tested in human myometrium as uterine tocolytics can advance the prevention of preterm birth.<\/jats:p>","DOI":"10.3390\/biom13061005","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T01:31:14Z","timestamp":1687138274000},"page":"1005","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["\u03b23 Receptor Signaling in Pregnant Human Myometrium Suggests a Role for \u03b23 Agonists as Tocolytics"],"prefix":"10.3390","volume":"13","author":[{"given":"Iain L. O.","family":"Buxton","sequence":"first","affiliation":[{"name":"Myometrial Function Group, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hazik","family":"Asif","sequence":"additional","affiliation":[{"name":"Myometrial Function Group, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott D.","family":"Barnett","sequence":"additional","affiliation":[{"name":"Myometrial Function Group, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2471\/BLT.08.062554","article-title":"The Worldwide Incidence of Preterm Birth: A Systematic Review of Maternal Mortality and Morbidity","volume":"88","author":"Beck","year":"2010","journal-title":"Bull. 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