The tonic smooth muscles of lower esophageal sphincter (LES) and internal anal sphincter (IAS) are subject to modulation by the neurohumoral agents. We report that angiotensin (Ang) II-induced contraction of rat IAS and LES smooth muscle cells (SMC) was Inhibited by Clostridium botulinum C3 exozyme, HA 1077 and Y 27632, suggesting a role for Rho kinase and a Rhoassociated kinase (ROK). Ang II-induced contraction of the SMC was also attenuated by genistein, antibodies to the pp60c-arc, p190 RhoGTPase-activating protein (p190 RhoGAP), carboxyl terminus of Gα13, carboxyl terminus peptide, and ADP ribosyiation factor (ARF) antibody. Ang II-induced increase in p190 RhoGAP tyrosine phosphorylation was attenuated by genistein. Furthermore, Ang II-induced increase in smooth muscle tone and phosphorylation of myosin light chain (MLC; 20 kDa; MLC20-P) were attenuated by Y 27632 and genlstein. The results suggest an important role for Gα13 and pp60c-arc in the Intracellular events responsible for the activation of RhoA/ROK in Ang II-induced contraction of LES and IAS SMC.
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