Activation of Rho signaling contributes to lysophosphatidic acid-induced contraction of intact ileal smooth muscle of guinea-pig

To elucidate the possible role of Rho A/Rho-kinase on lysophosphatidic acid (LPA)-induced contraction in intact guinea-pig ileal smooth muscle, we exa mined effects of pretreatment with a specific inhibitor of Rho-kinase (Y-27 632) on the LPA-induced contraction and MLC20 phosphorylation. In addition, we investigated whether LPA actually elicits an activation of Rho A by stu dying subcellular distribution of Rho A in unstimulated and stimulated smoo th muscles by LPA. LPA induced a less intense, but sustained, contraction c ompared with ACh, and was accompanied by significant increases in MLC20 pho sphorylation. The effects of LPA on tension and MLC20 phosphorylation were inhibited by Y-27632. The ACh-induced contraction, but not increases in MLC 20 phosphorylation, was partially inhibited by Y-27632. High K+-induced con traction was unaffected by the inhibitor. LPA stimulated translocation of R ho A from the cytosol to the membrane fraction of the muscle. Translocation of Rho A was also induced by ACh and high K+. These results suggest that L PA-induced contraction of intact ileal smooth muscle is dominated through a ctivation of Rho A and Rho-kinase and subsequent increases in MLC20 phospho rylation.