{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:04:06Z","timestamp":1783555446353,"version":"3.55.0"},"reference-count":33,"publisher":"The Endocrine Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human myometrial contraction plays a fundamental role in labor. Dysfunction of uterine contraction is an important cause of labor progression failure. Although the mechanisms controlling uterine contraction are not completely understood, intracellular Ca2+ mobilization plays an important role during uterine contraction. Several mechanisms of intracellular Ca2+ mobilization are present in smooth muscle, but in the human uterus, only 1,4,5-trisphosphate-induced Ca2+ release has been studied extensively. Ryanodine receptor channels are present in myometrium. We determined the role of the cyclic ADP-ribose (cADPR)-signaling pathway in oxytocin-induced intracellular Ca2+ [(Ca2+)i] transients in human myometrial cells. We found that oxytocin-induced Ca2+ transient is dependent on several sources of Ca2+, including extracellular Ca2+ and intracellular Ca2+ stores. In addition, we found that both the 1,4,5-trisphosphate- and the cADPR-induced Ca2+ releasing systems are important for the induction of [Ca2+]i transients by oxytocin in human myometrial cells. Furthermore, we investigated TNF\u03b1 regulation of oxytocin-induced [Ca2+]i transients, CD38 cyclase activity, and CD38 expression in human myometrial cells. We found that oxytocin-induced [Ca2+]i transients were significantly increased by 50 ng\/ml TNF. Similarly, CD38 mRNA levels, CD38 expression, and cyclase activity were increased by TNF\u03b1, thus increasing cADPR levels. We propose that a complex interaction between multiple signaling pathways is important for the development of intracellular Ca2+ transients induced by oxytocin and that TNF\u03b1 may contribute for the myometrium preparation for labor by regulating the cADPR-signaling pathway. The observation that the cADPR-signaling pathway is important for the development of intracellular Ca2+ transients in human myometrial cells raises the possibility that this signaling pathway could serve as a target for the development of new therapeutic strategies for abnormal myometrial contraction observed during pregnancy.<\/jats:p>","DOI":"10.1210\/en.2003-0774","type":"journal-article","created":{"date-parts":[[2003,10,21]],"date-time":"2003-10-21T00:22:02Z","timestamp":1066695722000},"page":"881-889","source":"Crossref","is-referenced-by-count":72,"title":["The Role of Cyclic-ADP-Ribose-Signaling Pathway in Oxytocin-Induced Ca2+ Transients in Human Myometrium Cells"],"prefix":"10.1210","volume":"145","author":[{"given":"Hosana","family":"Barata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Thompson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weronika","family":"Zielinska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young S.","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos B.","family":"Mantilla","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yedatore S.","family":"Prakash","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Feitoza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Sieck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo N.","family":"Chini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071612473710900_R1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1113\/eph8602178","volume":"86","author":"Bernal,","journal-title":"Exp Physiol"},{"key":"2020071612473710900_R2","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/S0140-6736(02)11476-0","article-title":"Preterm delivery.","volume":"360","author":"Slattery","year":"2002","journal-title":"Lancet"},{"key":"2020071612473710900_R3","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1113\/eph8602180","article-title":"Regulation of human myometrial contraction during pregnancy and labour: are calcium homeostatic pathways important?","volume":"86","author":"Tribe","year":"2001","journal-title":"Exp Physiol"},{"key":"2020071612473710900_R4","first-page":"169","article-title":"Intracellular signaling and phasic myometrial contractions.","volume":"5","author":"Phillippe","year":"1998","journal-title":"J Soc Gynecol Invest"},{"key":"2020071612473710900_R5","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/S1071-5576(02)00169-7","article-title":"In vivo monitoring of intracellular free calcium changes during uterine activation by prostaglandin F-2\u03b1 and oxytocin.","volume":"9","author":"Ruttner","year":"1998","journal-title":"J Soc Gynecol Invest"},{"key":"2020071612473710900_R6","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1095\/biolreprod60.4.777","article-title":"Oxytocin-induced Ca2+ responses in human myometrial cells.","volume":"60","author":"Burghardt","year":"1999","journal-title":"Biol Reprod"},{"key":"2020071612473710900_R7","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/35036035","article-title":"The versatility and universality of calcium signalling.","volume":"1","author":"Berridge","year":"2000","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2020071612473710900_R8","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1042\/bj3220777","article-title":"Differential expression of ryanodine receptor RyR2 mRNA in the non-pregnant and pregnant human myometrium.","volume":"322","author":"Awad","year":"1997","journal-title":"Biochem J"},{"key":"2020071612473710900_R9","first-page":"C243","author":"Martin","year":"1999"},{"key":"2020071612473710900_R10","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1054\/ceca.1999.0056","article-title":"Focal sarcoplasmic reticulum calcium stores and diffuse inositol 1,4,5-trisphosphate and ryanodine receptors in human myometrium.","volume":"26","author":"Young","year":"1999","journal-title":"Cell Calcium"},{"key":"2020071612473710900_R11","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1067\/mob.2001.113872","article-title":"The mechanism of propagation of intracellular calcium waves in cultured human uterine myocytes.","volume":"184","author":"Young","year":"2001","journal-title":"Am J Obstet Gynecol"},{"key":"2020071612473710900_R12","first-page":"43","author":"Chini","year":"2001"},{"key":"2020071612473710900_R13","doi-asserted-by":"crossref","first-page":"C1485","DOI":"10.1152\/ajpcell.1994.266.6.C1485","article-title":"Structure and function of ryanodine receptors","volume":"266","author":"Coronado","year":"1994","journal-title":"Am J Physiol"},{"key":"2020071612473710900_R14","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/0962-8924(94)90104-X","article-title":"Ca2+ release induced by cyclic ADP ribose.","volume":"4","author":"Galione","year":"1994","journal-title":"Trends Cell Biol"},{"key":"2020071612473710900_R15","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1016\/S0021-9258(18)94230-4","article-title":"Structural determination of a cyclic metabolite of NAD+ with intracellular Ca2+-mobilizing activity.","volume":"264","author":"Lee","year":"1989","journal-title":"J Biol Chem"},{"key":"2020071612473710900_R16","doi-asserted-by":"crossref","first-page":"5872","DOI":"10.1073\/pnas.94.11.5872","article-title":"Effect of estrogen upon cyclic ADP ribose metabolism: \u03b2-estradiol stimulates ADP ribosyl cyclase in rat uterus.","volume":"94","author":"Chini","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612473710900_R17","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/S0003-9861(02)00486-1","article-title":"The cyclic-ADP-ribose signaling pathway in human myometrium.","volume":"407","author":"Chini","year":"2002","journal-title":"Arch Biochem Biophys"},{"key":"2020071612473710900_R18","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1042\/bj3530531","article-title":"NAADP elicits specific microsomal Ca2+ release from mammalian cells.","volume":"353","author":"Yusufi","year":"2001","journal-title":"Biochem J (Lond)"},{"key":"2020071612473710900_R19","doi-asserted-by":"crossref","first-page":"H1482","DOI":"10.1152\/ajpheart.2000.279.4.H1482","article-title":"cADP ribose and [Ca(2+)](i) regulation in rat cardiac myocytes","volume":"279","author":"Prakash","year":"2000","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2020071612473710900_R20","doi-asserted-by":"crossref","first-page":"C1653","DOI":"10.1152\/ajpcell.1998.274.6.C1653","article-title":"Role of cyclic ADP-ribose in the regulation of [Ca2+]i in porcine tracheal smooth muscle","volume":"274","author":"Prakash","year":"1998","journal-title":"Am J Physiol"},{"key":"2020071612473710900_R21","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1161\/01.RES.86.11.1153","article-title":"ADP-ribosyl cyclase in rat vascular smooth muscle cells: properties and regulation.","volume":"86","author":"De Toledo","year":"2000","journal-title":"Circ Res"},{"key":"2020071612473710900_R22","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1042\/bj3620125","article-title":"CD38 is the major enzyme responsible for synthesis of nicotinic acid-adenine dinucleotide phosphate in mammalian tissues.","volume":"362","author":"Chini","year":"2002","journal-title":"Biochem J"},{"key":"2020071612473710900_R23","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/0014-5793(93)80279-4","article-title":"A novel ryanodine sensitive calcium release mechanism in cultured human myometrial smooth-muscle cells.","volume":"330","author":"Lynn","year":"1993","journal-title":"FEBS Lett"},{"key":"2020071612473710900_R24","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1590\/S0100-879X2002000500005","article-title":"Interactions between intracellular Ca2+stores: Ca2+ release from NAADP pool potentiates cADPR-induced Ca2+ release.","volume":"35","author":"Chini","year":"2002","journal-title":"Braz J Med Biol Res"},{"key":"2020071612473710900_R25","first-page":"F91","article-title":"cADPribose\/ryanodine channel\/Ca2+-release signal transduction pathway in mesangial cells","volume":"281","author":"Yusufi","year":"2001","journal-title":"Am J Physiol"},{"key":"2020071612473710900_R26","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1096\/fj.02-0450fje","article-title":"CD38\/cyclic-ADP-ribose-mediated Ca2+ signaling contributes to airway smooth muscle hyperresponsiveness.","volume":"17","author":"Deshpande","year":"2003","journal-title":"FASEB J"},{"key":"2020071612473710900_R27","doi-asserted-by":"crossref","first-page":"C741","DOI":"10.1152\/ajpcell.1995.268.3.C741","article-title":"Metabolism of cyclic ADP-ribose in opossum kidney renal epithelial cells","volume":"268","author":"Beers","year":"1995","journal-title":"Am J Physiol"},{"key":"2020071612473710900_R28","first-page":"985","author":"Challis","year":"1994"},{"key":"2020071612473710900_R29","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1113\/eph8602179","article-title":"Uterine contractility symposium: the Litchfield Lecture. Hormones and calcium: mechanisms controlling uterine smooth muscle contratile activity.","volume":"86","author":"Barbara","year":"2001","journal-title":"Exp Physiol"},{"key":"2020071612473710900_R30","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1053\/plac.2001.0782","article-title":"Cytokines of the placenta and extra-placental membranes: roles and regulation during human pregnancy and parturition.","volume":"23","author":"Bowen","year":"2002","journal-title":"Placenta"},{"key":"2020071612473710900_R31","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/molehr\/gag001","article-title":"Leukocyte density and pro-inflammatory cytokine expression in human fetal membranes, decidua, cervix and myometrium before and during labour at term.","volume":"9","author":"Osman","year":"2003","journal-title":"Mol Hum Reprod"},{"key":"2020071612473710900_R32","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1093\/humrep\/14.1.229","article-title":"Leukocytes infiltrate the myometrium during parturition: further evidence that labour is an inflammatory process.","volume":"14","author":"Thomson","year":"1999","journal-title":"Hum Reprod"},{"key":"2020071612473710900_R33","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1089\/jir.1996.16.941","article-title":"Antiviral nonspecific immunity of human placenta at term: possible role of endogenous tumor necrosis factor.","volume":"16","author":"Paradowska","year":"1996","journal-title":"J Interferon Cytokine Res"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/145\/2\/881\/9025568\/endo0881.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/145\/2\/881\/9025568\/endo0881.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T04:26:19Z","timestamp":1623471979000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/145\/2\/881\/2500669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,2,1]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2004,2,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2003-0774","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,2,1]]}}}