14563702

pubmed:Citation

2

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 TNFalpha 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 TNFalpha, 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 TNFalpha 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.

eng

AIM

MEDLINE

0013-7227

Print

NLM

881-9

pubmed-meshheading:14563702-ADP-ribosyl Cyclase, pubmed-meshheading:14563702-Adult, pubmed-meshheading:14563702-Antigens, CD, pubmed-meshheading:14563702-Antigens, CD38, pubmed-meshheading:14563702-Calcium, pubmed-meshheading:14563702-Cyclic ADP-Ribose, pubmed-meshheading:14563702-Female, pubmed-meshheading:14563702-Gene Expression, pubmed-meshheading:14563702-Humans, pubmed-meshheading:14563702-Inositol 1,4,5-Trisphosphate, pubmed-meshheading:14563702-Membrane Glycoproteins, pubmed-meshheading:14563702-Microsomes, pubmed-meshheading:14563702-Myometrium, pubmed-meshheading:14563702-Oxytocin, pubmed-meshheading:14563702-RNA, Messenger, pubmed-meshheading:14563702-Ryanodine Receptor Calcium Release Channel, pubmed-meshheading:14563702-Signal Transduction, pubmed-meshheading:14563702-Tumor Necrosis Factor-alpha, pubmed-meshheading:14563702-Uterine Contraction

The role of cyclic-ADP-ribose-signaling pathway in oxytocin-induced Ca2+ transients in human myometrium cells.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't