The nitric oxide synthase inhibitor, Ng-nitro-l-arginine-methyl-ester, attenuates the delay in gastric emptying induced by hyperglycaemia in healthy humans

Abstract The aim of this study was to determine whether the nitric oxide (NO) synthase inhibitor, N^g‐nitro‐l ‐arginine‐methyl‐ester (l ‐NAME), reverses the effects of acute hyperglycaemia on gastric emptying and antropyloroduodenal (APD) motility. The study had a four‐way randomized crossover (hyperglycaemia vs euglycaemia; l ‐NAME vs placebo) design in a clinical laboratory setting. Seven healthy volunteers [four males; age 30.3 ± 3.8 years; body mass index (BMI) 23.6 ± 1.2 kg m^?2] were the study subjects. After positioning a transnasal manometry catheter across the pylorus, the blood glucose concentration was maintained at either 15 or 5 mmol L^?1 using a glucose/insulin clamp. An intravenous infusion of l ‐NAME (180 μg kg^?1 h^?1) or placebo (0.9% saline) was commenced (T = ?30 min) and continued for 150 min. At T = ?2 min, subjects ingested a drink containing 50 g of glucose made up to 300 mL with water. Gastric emptying was measured using 3D ultrasound, and APD motility using manometry. Hyperglycaemia slowed gastric emptying (P < 0.05), and this effect was abolished by l ‐NAME. l ‐NAME had no effect on gastric emptying during euglycaemia. Hyperglycaemia suppressed fasting antral motility [motility index: 3.9 ± 0.8 (hyperglycaemia) vs 6.5 ± 0.6 (euglycaemia); P < 0.01]; l ‐NAME suppressed postprandial antral motility [motility index: 3.6 ± 0.2 (l ‐NAME) vs 5.1 ± 0.2 (placebo); P < 0.001]. Postprandial basal pyloric pressure was higher during hyperglycaemia (P < 0.001), and lower after administration of l ‐NAME (P < 0.001). Slowing of gastric emptying induced by hyperglycaemia is mediated by NO, and may involve the modulation of tonic pyloric activity.     

Differential expression of P2X-purinoceptor subtypes in circular and longitudinal muscle of canine colon

Adenosine triphosphate (ATP) mediates excitatory junction potentials through P2X receptors in many smooth muscles. However, relatively little is known about postjunctional intestinal P2X receptors. We examined the effect of exogenous ATP on circular and longitudinal myocytes of canine colon using the patch clamp technique at 32 degrees C. In both cell types, ATP induced inward currents (I(ATP)) at -70 mV in a concentration-dependent manner. The potency profile of ATP analogues in circular myocytes was: ATP approximately 2-methylthio-ATP > alpha,beta-methylene ATP, and that in longitudinal myocytes was: alpha,beta-methylene ATP approximately ATP > 2-methylthio-ATP. Pretreatment of circular myocytes with alpha,beta-methylene ATP inhibited the response to subsequent ATP, suggesting receptor desensitization. I-V relationships of I(ATP) were linear with inward rectification and E(rev) of -13 mV. I(ATP) at -70 mV was carried predominantly by Na+ as determined by shifts in E(rev) when extracellular Na+ was lowered. In RT-PCR, circular myocytes expressed mRNAs encoding P2X2, 3 and 4, while longitudinal myocytes expressed mRNAs for P2X3 and 5. P2X7 was absent in both cells. Fragments of each subtype were cloned and sequenced. We failed to clone P2X1 and P2X6 genes. Overall, different P2X receptor subtypes are expressed in circular and longitudinal canine colonic myocytes. Their activation produces non-selective cation currents that can depolarize and excite muscles of both layers.     

Dietary factors in functional dyspepsia

Functional dyspepsia (FD) is characterized by upper gastrointestinal symptoms, which are frequently exacerbated by meal ingestion. While subgroups of FD patients exhibit a range of disturbances in upper gastrointestinal motor function, including delayed gastric emptying and abnormal intragastric meal distribution, which may reflect impaired proximal gastric relaxation and/or antral dysmotility, the association between symptoms and abnormalities in motor function appears to be relatively weak. More recently, the concept of visceral hypersensitivity to mechanical and chemical/nutrient stimuli has been promoted as important in the aetiology of dyspeptic symptoms. Somewhat surprisingly, the role of 'dietary' factors, that is, those factors, related directly to food ingestion, including patterns of nutrient intake, potential intolerance to specific foods or macronutrients, as well as cognitive factors, have been largely ignored. Moreover, presently available treatments fail to take into account the fact that symptoms are frequently induced by eating. This review focuses on the relevance of 'dietary' factors to FD.     

Measurements of gastric emptying of low- and high-nutrient liquids using 3D ultrasonography and scintigraphy in healthy subjects

Scintigraphy represents the 'gold standard' for the measurement of gastric emptying. Recent studies suggest that three-dimensional (3D) ultrasonography may allow a precise measure of gastric emptying, given the capacity for accurate volume calculations of the stomach. The aim of this study was to compare measurements of gastric emptying of both low- and high-nutrient drinks by 3D ultrasonography with scintigraphy. Ten healthy young subjects (6M, 4F, age 23.5 +/- 1.5 years) were studied on 2 days. Concurrent measurements of gastric emptying by scintigraphy and 3D ultrasonography were performed after ingestion of 500 mL beef soup (12 kcal) or 300 ml dextrose (25% w/v) (314 kcal) labelled with 20 MBq (99m)Tc-sulphur colloid. There was no significant difference between scintigraphic and ultrasonographic 50% emptying times (T50s) (soup: 27.7 +/- 4.8 min vs 23.8. +/- 4.8 min; dextrose: 122.2 +/- 13.3 min vs 131.9 +/- 10.2 min). There was a close correlation between scintigraphic and ultrasonographic T50s for both soup (r = 0.92, P = 0.0005) and dextrose (r = 0.88, P = 0.0007). For the T50s, the limits of agreement were -15.2 min and +8.1 min for the soup (mean difference -3.6 min) and -35.3 min and +47.6 min for dextrose (mean difference +6.2 min). 3D ultrasonography provides a valid measure of gastric emptying of liquid meals in healthy subjects.