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) 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 (12) Citing Articles via Google Scholar Google Scholar Articles by Xiao, D. Articles by Zhang, L. Search for Related Content PubMed PubMed Citation Articles by Xiao, D. Articles by Zhang, L.

ERK-mediated uterine artery contraction: role of thick and thin filament regulatory pathways

Center for Perinatal Biology, Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, California 92350

Submitted 16 October 2003 ; accepted in final form 16 December 2003

We have demonstrated that extracellular signal-regulated kinase (ERK) plays an important role in the regulation of uterine artery contraction. The present study tested the hypothesis that ERK regulates thick and thin filament regulatory pathways in the uterine artery. Isometric tension, intracellular free Ca²⁺ concentration ([Ca²⁺]_i), and 20-kDa myosin light chain (LC₂₀) phosphorylation were measured simultaneously in uterine arteries isolated from near-term (140 days gestation) pregnant sheep. Phenylephrine produced time-dependent increases in [Ca²⁺]_i and LC₂₀ phosphorylation that preceded the contraction, which were inhibited by the MEK (ERK) inhibitor PD-098059. In addition, PD-098059 decreased the intercept of the regression line of LC₂₀ phosphorylation vs. [Ca²⁺]_i but increased the rate of tension development vs. LC₂₀ phosphorylation. In contrast to phenylephrine, phorbol 12,13-bibutyrate (PDBu) produced contractions without changing [Ca²⁺]_i or LC₂₀ phosphorylation. PD-098059 potentiated PDBu-induced contractions without affecting [Ca²⁺]_i and LC₂₀ phosphorylation. PDBu produced time-dependent increases in phosphorylation of p42 and p44 ERK and ERK-dependent phosphorylation of caldesmon at Ser⁷⁸⁹ in the uterine artery. PD-098059 blocked PDBu-mediated phosphorylation of p42 and p44 ERK and caldesmon. The results indicate that ERK may regulate force by a dual regulation of thick and thin filaments in uterine artery smooth muscle. ERK potentiates the thick filament regulatory pathway by enhancing LC₂₀ phosphorylation via increases in [Ca²⁺]_i and Ca²⁺ sensitivity of LC₂₀ phosphorylation. In contrast, ERK attenuates the thin filament regulatory pathway and suppresses contractions independent of changes in LC₂₀ phosphorylation in the uterine artery.

isometric tension; intracellular free calcium concentration; myosin light chain phosphorylation; PD-098059; phenylephrine; phorbol 12,13-dibutyrate

This article has been cited by other articles:

				H. Zhang, D. Xiao, L. D. Longo, and L. Zhang Regulation of {alpha}1-adrenoceptor-mediated contractions of uterine arteries by PKC: effect of pregnancy Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2282 - H2289. [Abstract] [Full Text] [PDF]

				S. Somara and K. N. Bitar Phosphorylated HSP27 modulates the association of phosphorylated caldesmon with tropomyosin in colonic smooth muscle Am J Physiol Gastrointest Liver Physiol, October 1, 2006; 291(4): G630 - G639. [Abstract] [Full Text] [PDF]

				A. Maeda, Y.-i. Ozaki, S. Sivakumaran, T. Akiyama, H. Urakubo, A. Usami, M. Sato, K. Kaibuchi, and S. Kuroda Ca-independent phospholipase A2-dependent sustained Rho-kinase activation exhibits all-or-none response. Genes Cells, September 1, 2006; 11(9): 1071 - 1083. [Abstract] [Full Text] [PDF]

				D. Xiao, X. Huang, L. D. Longo, W. J. Pearce, and L. Zhang Regulation of baseline Ca2+ sensitivity in permeabilized uterine arteries: effect of pregnancy Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H413 - H420. [Abstract] [Full Text] [PDF]

				D. Xiao, J. N. Buchholz, and L. Zhang Pregnancy attenuates uterine artery pressure-dependent vascular tone: role of PKC/ERK pathway Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2337 - H2343. [Abstract] [Full Text] [PDF]

				Y. Zhao, L. Zhang, and L. D. Longo PKC-induced ERK1/2 interactions and downstream effectors in ovine cerebral arteries Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2005; 289(1): R164 - R171. [Abstract] [Full Text] [PDF]

				D. Xiao, L. D. Longo, and L. Zhang {alpha}1-Adrenoceptor-mediated phosphorylation of MYPT-1 and CPI-17 in the uterine artery: role of ERK/PKC Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2828 - H2835. [Abstract] [Full Text] [PDF]

				D. Xiao and L. Zhang Adaptation of uterine artery thick- and thin-filament regulatory pathways to pregnancy Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H142 - H148. [Abstract] [Full Text] [PDF]