PMID- 12388473 OWN - NLM STAT- MEDLINE DCOM- 20030114 LR - 20200930 IS - 0363-6119 (Print) IS - 0363-6119 (Linking) VI - 284 IP - 1 DP - 2003 Jan TI - ERK1/2-mediated phosphorylation of myometrial caldesmon during pregnancy and labor. PG - R192-9 AB - We used a timed-pregnant rat model to track changes in myometrial contractility during pregnancy and labor and to correlate these changes with upstream signaling events. Myometrium was harvested from CO(2)-euthanized rats. Although contraction amplitudes increased at 16 and 20 days of pregnancy, contraction incidence and area under the force curve were inhibited, consistent with the myometrial quiescence of pregnancy. The Ca(2+) sensitivity of contraction was decreased at 20 days of pregnancy and this was partially reversed in labor. The protein content of h-caldesmon (h-CaD) was increased in pregnancy. A 40-fold increase in the signal from a phospho-CaD antibody specific for phosphorylation at an ERK1/2 site occurred during labor. ERK1/2 activation increased significantly at the onset of labor. Myosin light chain phosphorylation (LC20-P) increased significantly in labor compared with the nonpregnant state. Thus we conclude that the increase in CaD protein content during pregnancy may contribute to a suppression of the contractility of pregnant myometrium. Conversely, CaD phosphorylation, through an ERK1/2-mediated signaling pathway, as well as an increase in basal LC20-P, is suggested to contribute to the reversal of inhibition and promote contraction of the uterus during labor. FAU - Li, Yunping AU - Li Y AD - Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. yli1@caregroup.harvard.edu FAU - Je, Hyun-Dong AU - Je HD FAU - Malek, Sabah AU - Malek S FAU - Morgan, Kathleen G AU - Morgan KG LA - eng GR - GM-07592/GM/NIGMS NIH HHS/United States GR - HL-31704/HL/NHLBI NIH HHS/United States GR - HL-42293/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. DEP - 20021003 PL - United States TA - Am J Physiol Regul Integr Comp Physiol JT - American journal of physiology. Regulatory, integrative and comparative physiology JID - 100901230 RN - 0 (Antibodies) RN - 0 (Calmodulin-Binding Proteins) RN - 0 (Myosin Light Chains) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Antibodies MH - Calcium/metabolism/pharmacology MH - Calmodulin-Binding Proteins/chemistry/*metabolism MH - Enzyme Activation MH - Female MH - Immunoblotting MH - Labor, Obstetric/*metabolism MH - Mitogen-Activated Protein Kinase 1/*metabolism MH - Mitogen-Activated Protein Kinase 3 MH - Mitogen-Activated Protein Kinases/*metabolism MH - Molecular Weight MH - Myometrium/drug effects/enzymology/*metabolism MH - Myosin Light Chains/chemistry/metabolism MH - Phosphorylation MH - Pregnancy MH - Rats MH - Rats, Sprague-Dawley MH - Uterine Contraction/metabolism EDAT- 2002/10/22 04:00 MHDA- 2003/01/15 04:00 CRDT- 2002/10/22 04:00 PHST- 2002/10/22 04:00 [pubmed] PHST- 2003/01/15 04:00 [medline] PHST- 2002/10/22 04:00 [entrez] AID - 00290.2002 [pii] AID - 10.1152/ajpregu.00290.2002 [doi] PST - ppublish SO - Am J Physiol Regul Integr Comp Physiol. 2003 Jan;284(1):R192-9. doi: 10.1152/ajpregu.00290.2002. Epub 2002 Oct 3.