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Long-chain fatty acids activate the free fatty acid receptor 1 (FFA1) and FFA4. In the gastrointestinal system, FFA1 and FFA4 have been found in the pancreas and intestine. Fatty food and decreased lower esophageal sphincter (LES) motility are associated with gastroesophageal reflux disease. The effect of long-chain fatty acids on the esophageal motility is unknown. The purpose of this study is to investigate the effects of long-chain fatty acids on the porcine LES motility ex vivo using isometric transducers. In endothelin 1-precontracted porcine LES strips, the FFA1 selective agonists, fasiglifam, TUG424, and GW9508, caused marked relaxations in a concentration-dependent manner. The relative efficacies to elicit relaxation were GW9508 > TUG424 > fasiglifam in both clasp and sling strips. In contrast, the FFA4 specific agonists, TUG891 and GSK137647, produced mild relaxations. In addition, the endogenous FFA1 agonist DHA caused a mild relaxation whereas GW1100, an FFA1 antagonist, inhibited GW9508 induced relaxation of the porcine LES clasp and sling muscle. Both real-time PCR and immunohistochemistry revealed that FFA1 and FFA4 were expressed in the porcine LES. Real-time PCR analysis showed that the FFA4 expression was much lower than FFA1. Taken together, long-chain fatty acid receptor agonists elicit relaxation of the porcine LES. FFA1 might influence LES motility.

Background: Drugs such as citalopram, "targeting" the serotonin pathway, can alter esophageal mechano‐chemical sensitivity and gastrointestinal motility. The aim of this study was to clarify the effect of citalopram on esophageal motility and sphincter function, transient lower esophageal sphincter relaxations (TLESRs), and reflux events. Methods: Sixteen healthy volunteers (HV) receiving 20 mg citalopram or placebo intravenously, in a randomized cross‐over fashion, underwent two high‐resolution impedance manometry studies involving liquid swallows and a high‐fat, high‐caloric meal. Manometric, reflux, and symptom‐related parameters were studied. Key Results: A lower distal contractile integral was recorded under citalopram, compared with placebo (P = 0.026). Upper esophageal sphincter (UES) resting pressure was significantly higher after citalopram administration throughout the study (P < 0.05, all periods). Similarly, the UES postswallow mean and maximum pressures were higher in the citalopram condition (P < 0.0001, in both cases) and this was also the case for the 0.2 s integrated relaxation pressure (P = 0.04). Esophagogastric junction resting pressures in the citalopram visit were significantly higher during swallow protocol, preprandial period, and the first postprandial hour (P < 0.05, in all cases). TLESRs and total reflux events were both reduced after citalopram infusion (P = 0.01, in both cases). During treatment with citalopram, five participants complained about globus sensation (P = 0.06). This citalopram‐induced globus was associated with higher UES postswallow mean and maximum pressure values (P = 0.01 and P = 0.04, respectively). Conclusions and Inferences: Administration of citalopram exerts a diversified response on esophageal motility and sphincter function, linked to clinically relevant phenomena: a reduction in postprandial TLESRs and the induction of drug‐induced globus. [ABSTRACT FROM AUTHOR]

Long-chain fatty acids activate the free fatty acid receptor 1 (FFA1) and FFA4. In the gastrointestinal system, FFA1 and FFA4 have been found in the pancreas and intestine. Fatty food and decreased lower esophageal sphincter (LES) motility are associated with gastroesophageal reflux disease. The effect of long-chain fatty acids on the esophageal motility is unknown. The purpose of this study is to investigate the effects of long-chain fatty acids on the porcine LES motility ex vivo using isometric transducers. In endothelin 1-precontracted porcine LES strips, the FFA1 selective agonists, fasiglifam, TUG424, and GW9508, caused marked relaxations in a concentration-dependent manner. The relative efficacies to elicit relaxation were GW9508 > TUG424 > fasiglifam in both clasp and sling strips. In contrast, the FFA4 specific agonists, TUG891 and GSK137647, produced mild relaxations. In addition, the endogenous FFA1 agonist DHA caused a mild relaxation whereas GW1100, an FFA1 antagonist, inhibited GW9508 induced relaxation of the porcine LES clasp and sling muscle. Both real-time PCR and immunohistochemistry revealed that FFA1 and FFA4 were expressed in the porcine LES. Real-time PCR analysis showed that the FFA4 expression was much lower than FFA1. Taken together, long-chain fatty acid receptor agonists elicit relaxation of the porcine LES. FFA1 might influence LES motility. [ABSTRACT FROM AUTHOR]

The lower esophageal sphincter (LES) is a specialized region of the esophageal smooth muscle that allows the passage of a swallowed bolus into the stomach. Nitric oxide (NO) plays a major role in LES relaxation. Nicorandil possesses dual properties of a NO donor and an ATP-sensitive potassium channel (KATP channel) agonist, and is expected to reduce LES tone. This study investigated the mechanisms underlying the effects of nicorandil on the LES. Rat LES tissues were placed in an organ bath, and activities were recorded using an isometric force transducer. Carbachol-induced LES contraction was significantly inhibited by KATP channel agonists in a concentration-dependent manner; pinacidil >> nicorandil ≈ diazoxide. Nicorandil-induced relaxation of the LES was prevented by pretreatment with glibenclamide, whereas NG-nitro-l-arginine methyl ester (l-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and iberiotoxin were ineffective at preventing nicorandil-induced LES relaxation. Furthermore, nicorandil did not affect high K+-induced LES contraction. Reverse-transcription polymerase chain reaction analysis and immunohistochemistry revealed expression of KCNJ8 (Kir6.1), KCNJ11 (Kir6.2), ABCC8 (SUR1) and ABCC9 (SUR2) subunits of the KATP channel in the rat lower esophagus. These findings indicate that nicorandil causes LES relaxation chiefly by activating the KATP channel, and that it may provide an additional pharmacological tool for the treatment of spastic esophageal motility disorders.

Objective: to determine the importance of a symptom of Schatzki ring.Material and methods. The results of examining 95 patients aged 62–92 years with the symptoms of dyspepsia in the Netanya State Geriatric Center (Israel) in 1994–2004 were analyzed. Standard X-ray study of the upper digestive tract was complemented by provocation tests. The length of an X-ray-negative area (XNA) between barium in the esophagus and stomach and the width in the lower esophagus were measured.Results. Only 2 (2%) of the 95 patients were found to have normal function of the gastroesophageal junction (GEJ). Two patients with a drastic esophageal narrowing due to reflux esophagitis were excluded. The remaining (91) atients were divided into 2 groups. The width of the esophagus was less than 2 cm and 2 cm or more in 64 (70%) and 27 (30%) patients, respectively. In weak GEJ, there was esophageal dilatation above the XNA. When in a horizontal position, this portion of the esophagus evacuates its contents into the tomach as a result of ampullary function. It is proximally closed by ontracting the functional proximal sphincter (PS). When the ampulla contracts, its pressure increases up to the threshold. This causes the XNA to be closed and the ampulla to inject its contents into the stomach. The wider was the ampulla, the shorter the XNA was. Schatzki ring was detected in 20 (22%) of the 91 patients with gastroesophageal reflux disease (GERD). It was always at the level of the PS.Conclusion. The so-called sliding esophageal hernia is an esophageal mpulla measuring more than 2 cm in wide. The presence of the esophageal ampulla despite its size suggests that the GEJ is incompetent and GERD is present. Schatzki ring occurs at the level of the PS due to reflux esophagitis.

Sharon E Kim, Edy Soffer Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA Abstract: Patients with gastroesophageal reflux disease (GERD) who are not satisfied with acid suppression therapy can benefit primarily from fundoplication, a surgical intervention. Fundoplication has been the standard surgical procedure for GERD. It is effective but is associated with adverse effects, resulting in a declining number of interventions, creating a need for alternative interventions that are effective, yet have a better adverse effect profile. One such alternative involves the application of electrical stimulation to the lower esophageal sphincter. A number of animal studies showed that such stimulation can increase resting lower esophageal sphincter pressure. An acute human study confirmed this effect, and was followed by two open-label studies, with a follow-up of up to 3 years. Results thus far show that the therapy is associated with a significant improvement in symptoms, a significant reduction in esophageal acid exposure, and a very good safety profile. This review will describe the evolution of electrical stimulation therapy for GERD, as well as the safety and efficacy of this intervention. Keywords: gastroesophageal reflux disease, lower esophageal sphincter, health-related quality of life