Role ofpp60^c-srcandp^44/42MAPK in ANG II-induced contraction of rat tonic gastrointestinal smooth muscles

Abstract

(46, 49, 51). Limited information is available on the actions and signal transduction mechanisms of ANG II in the gastrointestinal smooth muscle, specifically the tonic smooth muscles of sphincters. Lower esophageal sphincter (LES) and internal anal sphincter (IAS) smooth muscles play an important role in the pathophysiology of a number of gastrointestinal motility disorders characterized either by the hypo-or hypertensive sphincteric smooth muscles (36,44).It is well known that a majority of the sphincteric smooth muscle tone may come from the myogenic properties of the smooth muscle (3,8,20). However, the basal tone of LES and IAS smooth muscles is prone to modulation by neurohumoral agents. Recent studies (41) conducted in our laboratory have shown that the rat is an appropriate animal model for investigating the actions of ANG II in the tonic smooth muscles of the IAS and LES. Our studies also show that the sphincteric smooth muscle contraction caused by ANG II is mediated primarily by its direct actions on the smooth muscle cells (SMC). ANG II-induced contraction of LES and IAS circular smooth muscles is inhibited specifically by the AT 1 antagonist losartan. This observation combined with the presence of AT 1 receptors in the LES and IAS smooth muscles suggests a specific role for AT 1 receptors in the mediation of ANG II-induced contraction in these tissues (16).The role of mitogen-activated protein kinase (p 44/42

Smooth muscle 22α facilitates angiotensin II-induced signaling and vascular contraction

“…We found that AngII induced a rapid elevation in phosphorylation of ERK1/2 and caldesmon. This is consistent with the previous studies in rat gastrointestinal smooth muscles [19]. AngIIevoked contraction in both VSMCs and aortic rings was attenuated by PD98059, indicating that AngIIinduced VSMC contraction was dependent on ERK1/2 activation.…”

Autocrine regulation of internal anal sphincter tone by renin-angiotensin system: comparison with phasic smooth muscle

“…In summary, present data combined with the potent contractile effect of ANG II (17,27,33), presence of AT 1 -R (35), the corresponding signal transduction cascade (31,34) in the IAS SMC, and fall in the IAS tone by ANG II biosynthesis inhibitors suggest that RAS, in part, may regulate basal tone in the IAS. The other extracellular signals for the balance of the basal tone may be prostanoids (6,7).…”

“…Earlier studies in the IAS have demonstrated the presence of ANG II and AT 1 receptors (14,17,31). However, the major part of the RAS in the IAS SMC has not been investigated.…”

“…These concepts have been proposed in certain hypertensive smooth muscles under pathophysiological conditions (28). The concept has, however, been not tested in the spontaneously tonic smooth muscles such as the IAS.Earlier studies in the IAS have demonstrated the presence of ANG II and AT 1 receptors (14,17,31). However, the major part of the RAS in the IAS SMC has not been investigated.…”

Characterization of protein kinase pathways responsible for Ca2+sensitization in rat ileal longitudinal smooth muscle

“…ERK1/2 and p38 MAPK have been previously reported to play a role in contraction of both vascular (37,41) and intestinal smooth muscle (6). The phosphorylation of caldesmon and/or calponin is thought to be one mechanism whereby ERK1/2 contributes to smooth muscle contraction (26,31).…”