Involvement of mast cells in basal and neurotensin-induced intestinal absorption of taurocholate in rats

Abstract

Neurotensin (NT), a hormone released from intestine by ingested fat, facilitates lipid digestion by stimulating pancreatic secretion and slowing the movement of chyme. In addition, NT can contract the gall bladder and enhance the enterohepatic circulation (EHC) of bile acids to promote micelle formation. Our recent finding that NT enhanced and an NT antagonist inhibited [(3)H]taurocholate ([(3)H]TC) absorption from proximal rat small intestine indicated a role for endogenous NT in the regulation of EHC. Here, we postulate the involvement of intestinal mast cells in the TC uptake process and in the stimulatory effect of NT. In anesthetized rats with the bile duct cannulated for bile collection, infusion of NT (10 pmol.kg(-1).min(-1)) enhanced the [(3)H]TC recovery rate from duodenojejunum by 2.2-fold. This response was abolished by pretreatment with mast cell stabilizers (cromoglycate, doxantrazole) and inhibitors of mast cell mediators (diphenhydramine, metergoline, zileuton). In contrast, mast cell degranulators (compound 48/80, substance P) and mast cell mediators (histamine, leukotriene C(4)) reproduced the effect of NT. N(G)-nitro-l-arginine methyl ester enhanced and l-arginine inhibited basal and NT-induced TC uptake, consistent with the known inhibitory effect of nitric oxide (NO) on mast cell reactivity. These results argue that basal and NT-stimulated TC uptake in rat jejunum are similarly dependent on mast cells, are largely mediated by release of mast cell mediators, and are subject to regulation by NO.