HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/2/R328    most recent 00042.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Li, Y. Articles by Morgan, K. G. Search for Related Content PubMed PubMed Citation Articles by Li, Y. Articles by Morgan, K. G.

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Role of ERK1/2 in uterine contractility and preterm labor in rats

Departments of ¹Anesthesia and Critical Care and ²Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston 02215; and ³Boston Biomedical Research Institute, Watertown, Massachusetts 02472

Submitted 20 January 2004 ; accepted in final form 1 April 2004

The present study tested the hypothesis that ERK activation is an essential step in the onset of labor in a rat model of preterm labor. The administration of RU-486, an antiprogesterone agent, to rats induced preterm delivery 22.2 ± 0.24 h after treatment. Changes in basal signaling events were studied in myometrial tissue from CO₂-euthanized rats. Rats treated with RU-486 displayed a dramatically increased in vitro uterine contractility compared with gestational stage-matched, sham-treated rats. In vitro contractility was not significantly different from that during spontaneous labor. During RU-486-induced preterm labor, as previously described for spontaneous labor, ERK phosphorylation levels increased, as did phosphorylation of caldesmon at Ser⁷⁸⁹, an ERK phosphorylation site. Also, a small but significant increase in 20-kDa myosin light chain phosphorylation was seen at a constant intracellular pCa of 7. When rats were chronically treated with an agent that prevents ERK activation, U-0126, the onset of RU-486-induced preterm labor was delayed in a statistically significant manner. Chronic in vivo treatment with U-0126 also significantly inhibited the RU-486-induced increase in in vitro contractility and ERK and caldesmon phosphorylation but did not alter the RU-486-induced increase in 20-kDa myosin light chain phosphorylation. These data indicate that ERK activation is a component of the multiple events leading to the development of labor in this rat model. We suggest that the ERK pathway could possibly be used to identify targets for the development of a novel class of tocolytic agents.

caldesmon; RU-486; smooth muscle; ERK inhibitor

This article has been cited by other articles:

				I. Garcia-Verdugo, Z. Tanfin, E. Dallot, M.-J. Leroy, and M. Breuiller-Fouche Surfactant Protein A Signaling Pathways in Human Uterine Smooth Muscle Cells Biol Reprod, August 1, 2008; 79(2): 348 - 355. [Abstract] [Full Text] [PDF]

				Z. Zeng, M. C. Velarde, F. A. Simmen, and R. C.M. Simmen Delayed Parturition and Altered Myometrial Progesterone Receptor Isoform A Expression in Mice Null for Kruppel-Like Factor 9 Biol Reprod, June 1, 2008; 78(6): 1029 - 1037. [Abstract] [Full Text] [PDF]

				I. Garcia-Verdugo, D. Leiber, P. Robin, E. Billon-Denis, R. Chaby, and Z. Tanfin Direct Interaction of Surfactant Protein A with Myometrial Binding Sites: Signaling and Modulation by Bacterial Lipopolysaccharide Biol Reprod, April 1, 2007; 76(4): 681 - 691. [Abstract] [Full Text] [PDF]

				M. A. Giembycz and R. Newton Beyond the dogma: novel {beta}2-adrenoceptor signalling in the airways. Eur. Respir. J., June 1, 2006; 27(6): 1286 - 1306. [Abstract] [Full Text] [PDF]