{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:04:04Z","timestamp":1790481844701,"version":"4.1.0"},"reference-count":40,"publisher":"The Endocrine Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Oxytocin (OT) receptors are important regulators of myometrial contractility. By using the activity of large conductance Ca2+-activated K+ (BKCa) channels as readout, we analyzed OT signaling in cells from nonpregnant (NPM) and pregnant (PM) rat myometrium in detail. In nystatin-perforated whole-cell patches from NPM cells, which leave the intracellular integrity intact, OT transiently increased BKCa-mediated outward currents (Iout). This OT-evoked Iout was caused by the Ca2+ transients in response to the Gq\/11-mediated activation of phospholipase C and was inhibited by activation of protein kinase A (PKA). In an open-access whole-cell patch (OAP), the OT-induced transient rise in Iout was disrupted whereas the regulation of BKCa by the cAMP\/PKA cascade remained intact. OT counteracted the isoprenaline, i.e. the \u03b2-adrenoceptor\/Gs-mediated effect in NPM cells measured in OAP. In contrast, OT further enhanced the \u03b2-adrenoceptor\/Gs-mediated effect on BKCa activity in PM cells. All OT effects in the OAP were mediated by pertussis toxin-sensitive Gi proteins and PKA. By quantitative real-time PCR and overexpression of the recombinant protein, we demonstrate that an up-regulation of the G\u03b2\u03b3-stimulated adenylyl cyclase II during pregnancy is most likely responsible for this switch. By studying the OT-evoked Iout in nystatin-perforated whole-cell patches of PM cells, we further detected that the OT receptor\/Gi\u03b2\u03b3-mediated coactivation of adenylyl cyclase II enhanced the \u03b2-adrenoceptor\/Gs-induced suppression of the OT-evoked Ca2+ transients and thus diminishes and self-limits OT-induced contractility. The differential regulation of the PKA-mediated suppression of OT-evoked Ca2+ transients and BKCa activity likely supports uterine quiescence during pregnancy.<\/jats:p>","DOI":"10.1210\/me.2006-0220","type":"journal-article","created":{"date-parts":[[2006,12,15]],"date-time":"2006-12-15T01:39:59Z","timestamp":1166146799000},"page":"740-752","source":"Crossref","is-referenced-by-count":49,"title":["Oxytocin Receptors Differentially Signal via Gq and Gi Proteins in Pregnant and Nonpregnant Rat Uterine Myocytes: Implications for Myometrial Contractility"],"prefix":"10.1210","volume":"21","author":[{"given":"Xiao-Bo","family":"Zhou","sequence":"first","affiliation":[{"name":"Institut fu\u0308r Pharmakologie fu\u0308r Pharmazeuten (X.-B.Z., F.S., M.K.), Universita\u0308tsklinikum Hamburg-Eppendorf, D-20246 Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Lutz","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Experimentelle und Klinische Pharmakologie und Toxikologie (S.L., T.W.), Medizinische Fakulta\u0308t Mannheim, Universita\u0308t Heidelberg, D-68169 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Steffens","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Pharmakologie fu\u0308r Pharmazeuten (X.-B.Z., F.S., M.K.), Universita\u0308tsklinikum Hamburg-Eppendorf, D-20246 Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Korth","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Pharmakologie fu\u0308r Pharmazeuten (X.-B.Z., F.S., M.K.), Universita\u0308tsklinikum Hamburg-Eppendorf, D-20246 Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Wieland","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Experimentelle und Klinische Pharmakologie und Toxikologie (S.L., T.W.), Medizinische Fakulta\u0308t Mannheim, Universita\u0308t Heidelberg, D-68169 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071614004911300_R1","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/356526a0","article-title":"Structure and expression of a human oxytocin receptor.","volume":"356","author":"Kimura","year":"1992","journal-title":"Nature"},{"key":"2020071614004911300_R2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1210\/endo-124-1-17","article-title":"Changes in intracellular free calcium in isolated myometrial cells: role of extracellular and intracellular calcium and possible involvement of guanine nucleotide-sensitive proteins.","volume":"124","author":"Anwer","year":"1989","journal-title":"Endocrinology"},{"key":"2020071614004911300_R3","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1210\/jcem-71-5-1243","article-title":"Regulation of intracellular free calcium in human myometrial cells by prostaglandin F2\u03b1: comparison with oxytocin.","volume":"71","author":"Molna\u0301r","year":"1990","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614004911300_R4","first-page":"101","article-title":"Direct measurement of intracellular free calcium in cultured human puerperal myometrial cells stimulated by oxytocin: effects of extracellular calcium and calcium channel blockers.","volume":"77","author":"Tasaka","year":"1991","journal-title":"Obstet Gynecol"},{"key":"2020071614004911300_R5","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1210\/endo.136.4.7895660","article-title":"Oxytocin stimulates myometrial guanosine triphosphatase and phospholipase-C activities via coupling to G\u03b1q\/11.","volume":"136","author":"Ku","year":"1995","journal-title":"Endocrinology"},{"key":"2020071614004911300_R6","first-page":"E870","article-title":"Coupling of oxytocin receptor to G proteins in rat myometrium during labor: Gi receptor interaction.","volume":"272","author":"Strakova","year":"1997","journal-title":"Am J Physiol"},{"key":"2020071614004911300_R7","doi-asserted-by":"crossref","first-page":"3761","DOI":"10.1073\/pnas.69.12.3761","article-title":"Hormonal interactions in the uterus: inhibition of isoproterenol-induced accumulation of adenosine 3\u2032:5\u2032-cyclic monophosphate by oxytocin and prostaglandins.","volume":"69","author":"Bhalla","year":"1972","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614004911300_R8","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1016\/S0006-291X(71)80255-3","article-title":"Cyclic adenosine 3\u2032,5\u2032 monophosphate levels in rat myometrium under the influence of epinephrine, prostaglandins and oxytocin. 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