This study will test the hypothesis that the uterine relaxants relaxin, a polypeptide hormone, isoproterenol, a Beta-adrenergic agent, and D600, a Ca2+ channel blocker, achieve relaxation via a common pathway, i.e., decreased myosin light chain kinase (MLCKase) activity resulting in net dephosphorylation of the 20,000 d light chains of myosin (LC20), by altering intracellular free Ca2+ and/or MLCKase phosphorylation to different extents. The relationship between inhibition of contractions, LC20 phosphorylation (measured by 2D-PAGE), MLCKase activity and MLCKase phosphorylation (measured by immunoprecipitation) will be determined as a function of time and concentration-dependence for the three relaxants. The ability of these agents to change intracellular free Ca2+ will be measured with the fluorescent dye Quin 2. Other measurements include effects on Ca2+ efflux from cells, Na?Ca2+exchange. Na+/K+ ATPase, and inositol triphosphate formation. The relationship between Ca2+, CaM, MLCKase kinetic properties, and LC20 phosphorylation will be tested in skinned muscle preparations. Specific relationships defined in these studies will be explored in tissue from animals in different hormonal states. These studies should increase our understanding of the hormonal control of uterine contraction/relaxation processes.
| Kim, Paul Y; Zhong, Miao; Kim, Yoon-Sun et al. (2012) Long chain polyunsaturated fatty acids alter oxytocin signaling and receptor density in cultured pregnant human myometrial smooth muscle cells. PLoS One 7:e41708 |
| Ku, Chun-Ying; Murtazina, Dilyara A; Kim, Yoon-Sun et al. (2010) Changes in rat myometrial plasma membrane protein kinase A are confined to parturition. Reprod Sci 17:696-704 |
| Zhong, Miao; Murtazina, Dilyara A; Phillips, Jennifer et al. (2008) Multiple signals regulate phospholipase CBeta3 in human myometrial cells. Biol Reprod 78:1007-17 |
| Sanborn, Barbara M (2007) Hormonal signaling and signal pathway crosstalk in the control of myometrial calcium dynamics. Semin Cell Dev Biol 18:305-14 |
