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

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.)