Inhibition of gastric secretion relieves post-prandial urgency, diarrhea, and cramps in a variety of GI disorders

Abstract

While several endothelial cell adhesion molecules (CAM) have been implicated as mediators of the leukocyte-endothelial cell adhesion observed in inflamed microvessels, P-selectin appears to be the major CAM that accounts for the very rapid (minutes) leukocyte rolling observed in these vessels. P-selectin can be rapidly mobilized from a preformed storage pool (WeibelPalade bodies) within endothelial cells by different stimuli, including histamine, thrombin, hydrogen peroxide, and leukotrienes. The objective of this study was to determine whether bradykinin, a well-known participant in inflammatory reactions can elicit P-selectin expression in the gastrointestinal microvasculature. The dual radiolabelled antibody technique was used to quantify endothelial cell P-selectin expression in rat metentery, small intestine, large intestine, pancreas and stomach. Intraperitoneal administration of bradykinin (25-200 lag) induced a dose-dependent up-regulation of P-selectin in most of the gastrointestinal organs. The increased P-selectin in these vascular beds occured within 15 min after bradykinin administration; no increases were noted 3 hrs after bradykinin. In order to determine whether the bradykinin B 2 receptor mediates the increased P-selectin expression elicited by bradykinin, some animals were pretreated with a Bz-receptor antagonist (HOE). In all gastrointestinal organs, HOE completely prevented the bradykinin-induced increase in P-selectin expression. These findings indicate that bradykinin can mobilize the preformed pool of P-selectin in vascular endothelial ceils and that bradykinin-mediated P-selectin involves the engagement of B~-receptors. Supported by P01 DK43785