The cyclic-ADP-ribose signaling pathway in human myometrium.
Human myometrial contraction plays a fundamental role in labor. Dysfunction of uterine contraction is an important cause of failure in progression of labor. The mechanisms of control of uterine contractions are not completely understood. It appears that intracellular Ca(2+) mobilization may play an important role during uterine contraction. Several mechanisms of intracellular Ca(2+) mobilization have been described. However, in human uterus only the inositol 1,4,5-trisphosphate-induced Ca(2+) release has been extensively studied to date. In view of the identification of the presence of functional ryanodine channels in myometrium, we explored the role of the endogenous regulator of the ryanodine channel cyclic-ADP-ribose in human myometrial Ca(2+) regulation. Cyclic-ADP-ribose (cADPR) is a naturally occurring nucleotide implicated in the regulation of the gating properties of the ryanodine channel, in fact cADPR may be a second messenger that activates the ryanodine receptor. Here we explore the components of the cADPR system in human myometrium. We found that human myometrium contains all the components of the cADPR pathway including (1) cADPR-activated microsomal Ca(2+) release and (2) enzymes responsible for synthesis and degradation of cADPR and, furthermore, that intracellular levels of cADPR were detected in human myometrial tissue. These data indicate that the cADPR system is present and operational in human myometrial tissue. Further research is warranted to determine the role of this new signaling molecule in uterine contraction.
Chini
Eduardo N
EN
Department of Anesthesiology and Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, MN 55905, USA. Chini.eduardo@mayo.edu
Chini
Claudia C S
CC
Barata da Silva
Hosana
H
Zielinska
Weronika
W
D000328:Adult; D000368:Aged; D002118:Calcium / Q000378:metabolism; D036563:Cyclic ADP-Ribose / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D006801:Humans; D007700:Kinetics; D008861:Microsomes / Q000378:metabolism; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D015290:Second Messenger Systems
D019837:Ryanodine Receptor Calcium Release Channel; D036563:Cyclic ADP-Ribose; D002118:Calcium