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Am J Physiol Gastrointest Liver Physiol 283: G390-G399, 2002; doi:10.1152/ajpgi.00025.2002
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Vol. 283, Issue 2, G390-G399, August 2002

Role of pp60c-src and p44/42 MAPK in ANG II-induced contraction of rat tonic gastrointestinal smooth muscles

Rajinder N. Puri, Ya-Ping Fan, and Satish Rattan

Department of Medicine, Division of Gastroenterology and Hepatology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107

We examined the role of mitogen-activated protein kinase (p44/42 MAPK) in ANG II-induced contraction of lower esophageal sphincter (LES) and internal anal sphincter (IAS) smooth muscles. Studies were performed in the isolated smooth muscles and cells (SMC). ANG II-induced changes in the levels of phosphorylation of different signal transduction and effector proteins were determined before and after selective inhibitors. ANG II-induced contraction of the rat LES and IAS SMC was inhibited by genistein, PD-98059 [a specific inhibitor of MAPK kinases (MEK 1/2)], herbimycin A (a pp60c-src inhibitor), and antibodies to pp60c-src and p120 ras GTPase-activating protein (p120 rasGAP). ANG II-induced contraction of the tonic smooth muscles was accompanied by an increase in tyrosine phosphorylation of p120 rasGAP. These were attenuated by genistein but not by PD-98059. ANG II-induced increase in phosphorylations of p44/42 MAPKs and caldesmon was attenuated by both genistein and PD-98059. We conclude that pp60c-src and p44/42 MAPKs play an important role in ANG II-induced contraction of LES and IAS smooth muscles.

tonic smooth muscle; tyrosine kinase; tyrosine phosphorylation; p120 ras GTPase-activating protein; p190 rho GTPase-activating protein


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