Neurohumoral, hormonal, and drug receptors for the lower esophageal sphincter

The lower esophageal sphincter (LES) is a specialized structure present at the junction of the esophagus with the stomach.'"The LES keeps closed at rest and is responsible for a pressure barrier which separates the negative intrathoracic pressure in the esophagus from the above atmospheric pressure in the stomach, and it opens in response to swallowing to allow the passage of an ingested bolus into the stomach.l, * Impairment of closure of the sphincter at rest is thought to be an important factor in causing reflux esophagitis, and abnormalities in the degree, duration, and timing of sphincter relaxation is an important cause of dysphagia in patients with achalasia.ssIn recent years there has been considerable interest in the physiology and pharmacology of the LES in order to understand the pathophysiology of sphincter incompetence and achalasia, and to search for appropriate therapeutic agents for their treatment.4,5*10-14Because all neurotransmitters, hormones, or exogenous drugs produce their effects by binding with specific receptors,15-17 consideration of these receptors has been very useful in the study of both the pharmacology and physiology of the LES.Effects of an ever-increasing, potentially infinite, number of drugs are more easily understood when their actions are perceived in terms of a finite number of receptors.Information on the existence and precise location of these receptors is helpful in defining the mode of action of new drugs.Furthermore, characterization of the receptors using selective agonists or antagonists has enhanced our understanding of the nature of the neurons and neurotransmitters involved in the regulation of LES function. General Receptor ConceptsMany years ago, Langley15, l6 observed that when a motor nerve to a striated muscle was cut and allowed to degenerate, it was still possible to stimulate the