Up-regulation of Rnd1 during pregnancy serves as a negative-feedback control for Ca2+ sensitization of contractile elements in rat myometrium |
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Authors: | Kim Yoon-Sun Kim Bokyung Karaki Hideaki Hori Masatoshi Ozaki Hiroshi |
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Institution: | Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, 113-8657, Tokyo, Japan. |
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Abstract: | We investigated the role of Rnd1, a member of the small GTP-binding Rho protein family, in the change in Ca(2+) sensitivity of contractile element in rat myometrium at estrus, gestation, and postpartum stages. In the permeabilized muscles, GTPgammaS or carbachol with GTP increased Ca(2+) sensitivity of contractile force in non-pregnant myometrium at the estrus stage, whereas these stimuli were ineffective in pregnant myometrium at day 21. After postpartum, the reduced Ca(2+) sensitization was recovered. Semi-quantitative RT-PCR analysis indicated that the expressions of RhoA, ROCKI, and ROCKII were not significantly different between non-pregnant and pregnant myometria. In contrast, the expression of Rnd1 was increased during the course of pregnancy, reaching a maximal at day 21, and rapidly declined after the delivery. On the other hand, Ca(2+) sensitization of contractile elements was decreased during the progress in gestation. These results suggest that Rnd1 may have an important role as a negative-feedback control of uterine contraction during gestation through the inhibition of RhoA-mediated increase in the Ca(2+) sensitivity of contractile elements. |
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