Regulatory Mechanism Of Contraction And Relaxation Of The Lower Esophageal Sphincter In Human

The lower esophageal sphincter (LES) is a thickened region of the circular muscle layer of the distal esophagus, in human extending over an axial distance of 2–3 cm. Liebermann-Meffer proposed that the muscular equivalent of LES consists of a thickened inner circular muscle layer configured as semicircular or clasp fibers adjacent to the lesser curvature and sling like muscle bundles on the greater curvature side formed by long oblique gastric fibers. These separate muscle groups create a zone of high pressure(15-30mmHg) and maintain sphincter closure. In vivo studies using manometric catheter with three paired holes in the left and right orientations within LES have shown a significant radial asymmetry in the distribution of the high-pressure zone. The highest pressures were recoreded in the left lateral direction of LES region which was sling fibers. Blockade of muscarinic cholinergic transmission with atropine caused a significant reduction of LES in the left side of gastroesophageal junction. In vitro the sling is more sensitive to cholinergic stimulation, whereas the clasp muscle develops greater spontaneous tension. It is well known that the appropriate function of the LES is controlled by excitatory and inhibitory neuronal mechanisms that cause relaxation during swallowing and normally prevent reflux but permit vomiting and venting of gas. This study was conducted to study the pharmacological characteristics of muscarinic acetylcholine receptor subtypes (mAChRs) and nitric oxide (NO), and the expression of mAChRs and neuronal nitric oxide synthase (nNOS) in sling and clasp fibers, with the purpose of further understanding of the physiological and pharmacological characteristics of the LES, and providing theoretical bases for the clinical treatment of esophageal motility disorders.PartⅠPharmacological Characterization of Muscarinic Receptor...