Role of pp60 and p MAPK in ANG II-induced contraction of rat tonic gastrointestinal smooth muscles

Puri, Rajinder N., Ya-Ping Fan, and Satish Rattan. Role of pp60c-src and p44/42 MAPK in ANG II-induced contraction of rat tonic gastrointestinal smooth muscles. Am J Physiol Gastrointest Liver Physiol 283: G390–G399, 2002; 10.1152/ajpgi.00025.2002.—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.