Glucose and glutamine gavage increase portal vein nitric oxide metabolite levels via adenosine A2b activation.

Introduction: Postprandial intestinal hyperemia is a complex vascular response during nutrient absorption. Many mediators have been studied including enteric reflexes, GI hormones, and absorption-stimulated metabolic mediators such as pH and adenosine. We have shown that nitric oxide (NO) mediates premucosal arteriolar dilation during glucose absorption and that glucose-induced portal vein NO metabolite production requires adenosine A2b receptor activation. We hypothesize that Na+-linked absorption of l-glutamine or l-glycine might also stimulate NO release in the enteroportal circulation via adenosine A2b receptors.

Methods: Male Sprague-Dawley rats (190-220 g) were anesthetized with urethane/alpha-chloralose and cannulated for hemodynamic monitoring and blood sampling. A right paramedian abdominal incision was made for access to both the stomach (gavage) and the portal vein (blood sampling). Animals received intragastric nutrient gavage (saline, d-glucose, l-glutamine, racemic glycine, or oleic acid) with and without adenosine A2b receptor blockade. NO metabolites (NOx) were measured by a fluorescent modified-Greiss assay at baseline and 30 min after nutrient gavage.

Results: Glucose and glutamine gavage increased portal NOx levels compared to baseline, while glycine and oleic acid gavage did not. Adenosine A2b antagonism returned NOx levels to baseline in both glucose and glutamine gavage animals, but did not alter portal NOx levels in glycine- or oleic acid-treated animals.

Conclusions: These data suggest that nutrient-induced adenosine is involved in a signaling process from the intestinal epithelium to nitric oxide-producing cells elsewhere in the vasculature. Adenosine A2b receptors are required for NO production during Na+-linked glucose or glutamine absorption.