Figure 1 - Signal transduction for lower esophageal sphincter (LES) contraction in response to agonists.

From the following article

Signal transduction in lower esophageal sphincter circular muscle

Piero Biancani and Karen M. Harnett

GI Motility online (2006)



Contraction of LES cells by maximally effective dose of acetylcholine (ACh) is shown as an example of signal transduction in response to high doses of agonists. ACh-induced contraction is mediated by activation of M3 muscarinic receptors linked to Gq and to phosphatidylinositol-specific phospholipase C (PI-PLC), and production of inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG) from phosphatidylinositol bisphosphate (PIP2). IP3 causes release of Ca2+ from stores (ER=endoplasmic reticulum) at a concentration sufficient to cause activation of calmodulin (CAM). Ca2+-CAM activates myosin light chain kinase (MLC Kinase) and inhibits protein kinase C (PKC), inducing a contraction that is entirely CAM dependent. Ca2+-CAM–induced inhibition of PKC masks the presence of other factors that would otherwise contribute to activation of PKC. (Source: Harnett et al.,3 with permission from the American Physiological Society.)

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