ABSTRACT
Obesity is a global epidemic posing a significant burden on patients and healthcare systems. Gastroesophageal reflux disease is associated with obesity and its prevalence is also growing worldwide. Numerous bariatric surgeries and endoscopic procedures have arisen to assist with weight loss and management of obesity-related conditions. However, the effect of these interventions on reflux is variable and the evidence is often conflicting. To date, Roux-en-Y gastric bypass remains the gold-standard for attaining both reflux and weight loss management, however novel endoscopic techniques are quickly becoming more prevalent as an alternative to surgery. This review aims to summarize currently available endoscopic and surgical weight loss procedures and their impact on reflux symptoms while emphasizing areas requiring additional investigation.
ABSTRACT
BACKGROUND/AIMS: Lubiprostone, a chloride channel type 2 (ClC-2) activator, was thought to treat constipation by enhancing intestinal secretion. It has been associated with increased intestinal transit and delayed gastric emptying. Structurally similar to prostones with up to 54% prostaglandin E2 activity on prostaglandin E receptor 1 (EP1), lubiprostone may also exert EP1-mediated procontractile effect on intestinal smooth muscles. We investigated lubiprostone's effects on intestinal smooth muscle contractions and pyloric sphincter tone. METHODS: Isolated murine small intestinal (longitudinal and circular) and pyloric tissues were mounted in organ baths with modified Krebs solution for isometric recording. Basal muscle tension and response to electrical field stimulation (EFS; 2 ms pulses/10 V/6 Hz/30 sec train) were measured with lubiprostone (10(-10)-10(-5) M) +/- EP1 antagonist. Significance was established using Student t test and P < 0.05. RESULTS: Lubiprostone had no effect on the basal tension or EFS-induced contractions of longitudinal muscles. With circular muscles, lubiprostone caused a dose-dependent increase in EFS-induced contractions (2.11 +/- 0.88 to 4.43 +/- 1.38 N/g, P = 0.020) that was inhibited by pretreatment with EP1 antagonist (1.69 +/- 0.70 vs. 4.43 +/- 1.38 N/g, P = 0.030). Lubiprostone had no effect on circular muscle basal tension, but it induced a dose-dependent increase in pyloric basal tone (1.07 +/- 0.01 to 1.97 +/- 0.86 fold increase, P < 0.05) that was inhibited by EP1 antagonist. CONCLUSIONS: In mice, lubiprostone caused a dose-dependent and EP1-mediated increase in contractility of circular but not longitudinal small intestinal smooth muscles, and in basal tone of the pylorus. These findings suggest another mechanism for lubiprostone's observed clinical effects on gastrointestinal motility.