Tension receptors in the proximal stomach: Are they relevant to triggering of transient lower esophageal sphincter relaxations (TLESRs)?

Metabotropic glutamate receptors (mGluR) are classified into group I, II, and III mGluR. Group I (mGluR1, mGluR5) are excitatory, whereas group II and III are inhibitory. mGluR5 antagonism potently reduces triggering of transient lower esophageal sphincter relaxations and gastroesophageal reflux. Transient lower esophageal sphincter relaxations are mediated via a vagal pathway and initiated by distension of the proximal stomach. Here, we determined the site of action of mGluR5 in gastric vagal pathways by investigating peripheral responses of ferret gastroesophageal vagal afferents to graded mechanical stimuli in vitro and central responses of nucleus tractus solitarius (NTS) neurons with gastric input in vivo in the presence or absence of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP). mGluR5 were also identified immunohistochemically in the nodose ganglia and NTS after extrinsic vagal inputs had been traced from the proximal stomach. Gastroesophageal vagal afferents were classified as mucosal, tension, or tension-mucosal (TM) receptors. MPEP (1–10 μM) inhibited responses to circumferential tension of tension and TM receptors. Responses to mucosal stroking of mucosal and TM receptors were unaffected. MPEP (0.001–10 nmol icv) had no major effect on the majority of NTS neurons excited by gastric distension or on NTS neurons inhibited by distension. mGluR5 labeling was abundant in gastric vagal afferent neurons and sparse in fibers within NTS vagal subnuclei. We conclude that mGluR5 play a prominent role at gastroesophageal vagal afferent endings but a minor role in central gastric vagal pathways. Peripheral mGluR5 may prove a suitable target for reducing mechanosensory input from the periphery, for therapeutic benefit.

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Response of canine lower esophageal sphincter to gastric distension

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1990.259.3.g380 ◽

1990 ◽

Vol 259 (3) ◽

pp. G380-G385 ◽

Cited By ~ 11

Author(s):

S. J. Franzi ◽

C. J. Martin ◽

M. R. Cox ◽

J. Dent

Keyword(s):

Lower Esophageal Sphincter ◽

Gastric Wall ◽

Progressive Increase ◽

Truncal Vagotomy ◽

Gastric Distension ◽

Wall Tension ◽

Proximal Stomach ◽

Lower Esophageal Sphincter Relaxation ◽

Esophageal Sphincter ◽

Antral Distension

The aim of this study was to localize the region of the stomach responsible for triggering distension-induced transient lower esophageal sphincter relaxation (TLESR). The canine stomach was partitioned into subsegments by a row of buttressed sutures. This separated either the fundus from the lesser curve or the proximal stomach from the antrum. After 1 mo each region was progressively distended while gastroesophageal pressures were monitored. At the time of the first TLESR, gastric wall tension was estimated from the bag pressure and volume. Distension of the intact stomach, lesser curve, or proximal stomach in 12 dogs produced a progressive increase in lower esophageal sphincter (LES) pressure, which was interrupted at low gastric wall tension (29, 35, and 40 mmHg.cm, respectively) by a superimposed TLESR. Background LES pressure fell progressively with distension of the antrum but was unchanged by distension of the fundus alone. Both the fundus and antrum had significantly higher thresholds for triggering TLESR (96 and 105 mmHg.cm). In another two dogs truncal vagotomy performed at the time of gastric partitioning prevented both the change in background LES pressure, and the triggering of TLESR, associated with proximal gastric and antral distension. We conclude that the subcardiac region of the stomach is primarily responsible for triggering TLESR induced by distension and that the effect on background LES pressure depends on the region distended.

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Effect of prolonged gastric distension on motor function of LES and of proximal stomach

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00526.2001 ◽

2002 ◽

Vol 283 (3) ◽

pp. G677-G680 ◽

Cited By ~ 8

Author(s):

M. Allocca ◽

M. Mangano ◽

R. Penagini

Keyword(s):

Lower Esophageal Sphincter ◽

Motor Function ◽

Healthy Subjects ◽

Time Effect ◽

Gastric Distension ◽

Threshold Pressure ◽

Proximal Stomach ◽

Experimental Conditions ◽

Esophageal Sphincter ◽

Sensory Functions

Gastric distension is a potent stimulus of transient lower esophageal sphincter (LES) relaxation. To investigate the time effect of prolonged gastric distension on the rate of transient LES relaxations, LES pressure, and the motor and sensory functions of the proximal stomach, we performed a continuous isobaric distension of the proximal stomach at the 75% threshold pressure for discomfort for 2 h in seven healthy subjects. A multilumen assembly incorporating a sleeve and an electronic barostat was used. The rate of transient LES relaxations ( n/30 min) was constant during the first hour [4.1 ± 1.2 (0–30 min) and 5.4 ± 1.1 (30–60 min)] but markedly decreased ( P < 0.05) in the second hour [2.1 ± 0.5 (60–90 min) and 2.3 ± 0.9 (90–120 min)], whereas LES pressure, baseline volume and volume waves within the gastric bag, hunger, and fullness did not change throughout the experiment. It is concluded that the rate of transient LES relaxations decreases with time during prolonged gastric distension, thus suggesting that this type of stimulus should not be used in sequential experimental conditions.

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The Evolution of the Definition and Diagnosis of Barrett Esophagus: A Historical Perspective

Foregut: The Journal of the American Foregut Society ◽

10.1177/2634516121989879 ◽

2021 ◽

Vol 1 (1) ◽

pp. 16-23

Author(s):

Parakrama Chandrasoma

Keyword(s):

Lower Esophageal Sphincter ◽

Historical Perspective ◽

Squamous Epithelium ◽

Acid Exposure ◽

Barrett Esophagus ◽

Proximal Stomach ◽

The Future ◽

Columnar Metaplasia ◽

Esophageal Sphincter ◽

Definition Of

Historical definitions of Barrett esophagus (BE) have depended on 2 beliefs: the esophagus is a squamous lined tube and the stomach is a columnar lined sac. Norman Barrett, in 1957, recognized that columnar lining in the tubular esophagus was reflux-induced metaplasia of squamous epithelium, leading to the present definition of BE. Recent evidence that gastric overdistension results in acid exposure of distal esophageal squamous epithelium, causing progressive columnar metaplasia, damage to the lower esophageal sphincter, and dilatation of the abdominal esophagus. This is presently mistaken at endoscopy for proximal stomach. The future definition of BE will likely include intra-sphincteric BE.

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