Role of pp60(c-src) and p(44/42) MAPK in ANG II-induced contraction of rat tonic gastrointestinal smooth muscles

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2002-08, Vol.283 (2), p.G390-G399
• Main Authors: Puri, Rajinder N, Fan, Ya-Ping, Rattan, Satish
• Format: Article
• Language: English
• Subjects: Angiotensin II - pharmacology; Animals; Antibodies - pharmacology; Benzoquinones; Calmodulin-Binding Proteins - metabolism; Digestive System - drug effects; Digestive System Physiological Phenomena; Enzyme Inhibitors - pharmacology; Female; Flavonoids - pharmacology; Genistein - pharmacology; In Vitro Techniques; Lactams, Macrocyclic; Male; Mitogen-Activated Protein Kinase 1 - physiology; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases - physiology; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; p120 GTPase Activating Protein - immunology; p120 GTPase Activating Protein - pharmacology; Phosphorylation; Protein-Tyrosine Kinases - antagonists & inhibitors; Proto-Oncogene Proteins pp60(c-src) - antagonists & inhibitors; Proto-Oncogene Proteins pp60(c-src) - immunology; Proto-Oncogene Proteins pp60(c-src) - physiology; Quinones - pharmacology; Rats; Rats, Sprague-Dawley; Rifabutin - analogs & derivatives; Tyrosine - metabolism
• ISSN: 0193-1857
• DOI: 10.1152/ajpgi.00025.2002

We examined the role of mitogen-activated protein kinase (p(44/42) 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 pp60(c-src) inhibitor), and antibodies to pp60(c-src) and p(120) ras GTPase-activating protein (p(120) rasGAP). ANG II-induced contraction of the tonic smooth muscles was accompanied by an increase in tyrosine phosphorylation of p(120) rasGAP. These were attenuated by genistein but not by PD-98059. ANG II-induced increase in phosphorylations of p(44/42) MAPKs and caldesmon was attenuated by both genistein and PD-98059. We conclude that pp60(c-src) and p(44/42) MAPKs play an important role in ANG II-induced contraction of LES and IAS smooth muscles.