Related Experiment Video

Updated: Aug 18, 2026

In vitro Measurements of Tracheal Constriction Using Mice
10:20

In vitro Measurements of Tracheal Constriction Using Mice

Published on: June 25, 2012

Signal transduction pathways in esophageal and lower esophageal sphincter circular muscle

P Biancani1, U D Sohn, H G Rich

  • 1Department of Medicine, Rhode Island Hospital, Brown Medical School, Providence 02903, USA.

The American Journal of Medicine
|January 9, 1998
PubMed

Insights

Esophageal reflux involves distinct muscle contractions. Lower esophageal sphincter (LES) tone reduction in esophagitis alters signaling pathways, impacting LES pressure and potentially causing heartburn.

Area of Science:

  • Gastroenterology
  • Molecular Biology
  • Physiology

Background:

  • Esophageal reflux affects millions, potentially leading to serious complications like Barrett's esophagus.
  • Lower esophageal sphincter (LES) pressure impairment is common in chronic heartburn patients.
  • Esophagitis involves multifactorial causes, including LES relaxation and impaired esophageal clearance.

Purpose of the Study:

  • To investigate the distinct cellular mechanisms of acetylcholine (ACh)-induced contraction in esophageal and LES circular muscles.
  • To elucidate the role of calcium (Ca2+) sources and signal transduction pathways in LES pressure regulation.
  • To examine how experimental esophagitis affects LES tone and contraction signaling.

Main Methods:

  • Comparative analysis of Ca2+ sources and phospholipid metabolism in esophageal versus LES muscle.
  • Investigation of signal transduction pathways, including protein kinase C (PKC), calmodulin, and myosin light chain kinase.
  • Induction of experimental esophagitis to assess changes in basal LES tone and ACh-induced contraction pathways.

Main Results:

  • Esophageal muscle contraction relies on extracellular Ca2+ influx, phosphatidylcholine metabolism, and PKC activation.
  • LES muscle contraction primarily uses intracellular Ca2+ release (via phosphatidylinositol metabolism) and a calmodulin-myosin light chain kinase pathway.
  • Esophagitis induction reduced basal PI hydrolysis and intracellular Ca2+ stores, decreasing resting LES tone and shifting ACh signaling to an extracellular Ca2+-dependent PKC pathway.

Conclusions:

  • Distinct signaling pathways govern ACh-induced contractions in esophageal and LES muscles.
  • Impaired LES tone in esophagitis is linked to reduced intracellular Ca2+ signaling and a shift towards extracellular Ca2+ dependence.
  • These findings offer insights into the mechanisms underlying LES dysfunction and heartburn in reflux disease.

More Related Videos

Bladder Smooth Muscle Strip Contractility as a Method to Evaluate Lower Urinary Tract Pharmacology10:26

Bladder Smooth Muscle Strip Contractility as a Method to Evaluate Lower Urinary Tract Pharmacology

Published on: August 18, 2014

Utilizing the Precision-Cut Lung Slice to Study the Contractile Regulation of Airway and Intrapulmonary Arterial Smooth Muscle08:59

Utilizing the Precision-Cut Lung Slice to Study the Contractile Regulation of Airway and Intrapulmonary Arterial Smooth Muscle

Published on: May 5, 2022

Related Concept Videos

Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...
Fascicle Arrangement in Skeletal Muscles01:25

Fascicle Arrangement in Skeletal Muscles

Fascicles are bundles of muscle fibers in a skeletal muscle. Muscle fascicle arrangement is directly associated with the power and range of motion of various muscles. The configuration of these fascicles can vary, leading to different functional outcomes.
The four primary types of muscle based on fascicle arrangement are:
Parasympathetic Signaling01:30

Parasympathetic Signaling

Parasympathetic signaling plays a crucial role in regulating various physiological processes. It involves the release of acetylcholine (ACh) by parasympathetic neurons, which can have localized and short-lived effects. The majority of ACh released is rapidly inactivated at the synapse by the enzyme acetylcholinesterase (AChE), which hydrolyzes Ach into choline and acetate. Additionally, the tissue cholinesterase deactivates any ACh diffusing into the surrounding tissues.
The effects of...
Esophagus01:24

Esophagus

The esophagus, a muscular conduit linking the pharynx and stomach, measures roughly 10 inches (25.4 cm) and sits behind the trachea. It remains collapsed when not swallowing. The esophagus follows a predominantly straight path through the thoracic mediastinum and enters the abdominal cavity through a diaphragmatic opening known as the esophageal hiatus.
The movement of edibles from the pharynx into the esophagus is facilitated by the upper esophageal sphincter, which is formed primarily by the...
Esophageal Achalasia01:27

Esophageal Achalasia

Esophageal achalasia is a chronic neurogenic disorder characterized by impaired relaxation of the lower esophageal sphincter (LES) and absent or ineffective peristalsis in the distal esophagus. This leads to a functional obstruction without a physical blockage, despite significant disruption of esophageal motility.EtiologyAchalasia is caused by degeneration of the myenteric (Auerbach's) plexus, specifically the loss of inhibitory ganglion cells that produce vasoactive intestinal peptide (VIP)...