{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T18:11:50Z","timestamp":1761675110102},"reference-count":28,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:p>Oxytocin-induced Ca<jats:sup>2+<\/jats:sup>transients play an important role in myometrial contractions. Here, using a knockout model, we found that the enzyme CD38, responsible for the synthesis of the second messenger cyclic ADP-ribose (cADPR), plays an important role in the oxytocin-induced Ca<jats:sup>2+<\/jats:sup>transients and contraction. We also observed that CD38 is necessary for TNF-\u03b1-increased agonist-stimulated Ca<jats:sup>2+<\/jats:sup>transients in human myometrial cells. We provide experimental evidence that the TNF-\u03b1 effect is mediated by increased expression of the enzyme CD38. First, we observed that TNF-\u03b1 increased oxytocin-induced Ca<jats:sup>2+<\/jats:sup>transients and CD38 expression in human myometrial cells. Moreover, using small interference RNA technology, we observed that TNF-\u03b1 stimulation of agonist-induced Ca<jats:sup>2+<\/jats:sup>transients was abolished by blocking the expression of CD38. In control experiments, we observed that activation of the component of the TNF-\u03b1 signaling pathway, NF-\u03baB, was not affected by the treatments. Finally, we observed that the effects of TNF-\u03b1 on CD38 cyclase and oxytocin-induced Ca<jats:sup>2+<\/jats:sup>transients are abolished by progesterone. In conclusion, we provide the first experimental evidence that CD38 is important for myometrial Ca<jats:sup>2+<\/jats:sup>transients and contraction. Moreover, CD38 is necessary for the TNF-\u03b1-mediated augmentation of agonist-induced Ca<jats:sup>2+<\/jats:sup>transients in myometrial cells. We propose that the balance between cytokines and placental steroids regulates the expression of CD38 in vivo and cell responsiveness to oxytocin.<\/jats:p>","DOI":"10.1152\/ajpendo.00122.2004","type":"journal-article","created":{"date-parts":[[2004,9,1]],"date-time":"2004-09-01T00:25:21Z","timestamp":1093998321000},"page":"E1142-E1148","source":"Crossref","is-referenced-by-count":21,"title":["Role of CD38 in myometrial Ca<sup>2+<\/sup>transients: modulation by progesterone"],"prefix":"10.1152","volume":"287","author":[{"given":"Michael","family":"Thompson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hosana","family":"Barata da Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weronika","family":"Zielinska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas A.","family":"White","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey P.","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frances E.","family":"Lund","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary C.","family":"Sieck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo N.","family":"Chini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0774"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1113\/eph8602178"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2001.0782"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1124\/mol.65.5.1051"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-9861(02)00486-1"},{"key":"R6","unstructured":"Chini ENand De Toledo FGS.The new calcium-mobilizing nucleotides cyclic ADP-ribose and NAADP. 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