Endogenous neurotensin facilitates enterohepatic bile acid circulation by enhancing intestinal uptake in rats

Abstract

away. Endogenous neurotensin facilitates enterohepatic bile acid circulation by enhancing intestinal uptake in rats. Am J Physiol Gastrointest Liver Physiol 281: G1413-G1422, 2001.-Initial studies on the digestive hormone neurotensin (NT) showing that intestinal NT mRNA expression and blood levels were altered in rats fed chow containing bile acid (BA) and the BA chelator cholestyramine led us to investigate the role of NT in the enterohepatic circulation of BA. In fasted, anesthetized rats with common bile ducts cannulated for bile collection, intravenous NT infusion (10 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) enhanced BA output relative to control over 3 h in animals administered donor bile into the duodenum (30 l/min). This suggested that the effect of NT was on the return of BA from the intestine to the liver, which is rate determining in the normal process. In rats prepared as described above and administered

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

“…Intestinal uptake of [ 3 H]TC was measured in biliary fistula rats as described by us (25,26). The rate of appearance of [ 3 H]TC in bile was equated with the rate of intestinal uptake, because this is the rate-determining step (26). Briefly, rats were fasted 24 h and anesthetized with ketamine-xylazine (60:10 mg/kg ip).…”

“…Infusion of NT into fasted rats, at doses giving near physiological blood levels, specifically enhanced intestinal absorption of taurocholate (TC), the primary conjugated BA, without altering that for cholic acid, its unconjugated counterpart (25). More importantly, infusion of NT antagonist SR-48692 inhibited intestinal TC absorption, suggesting a role for endogenous NT in this process (26). The effect of NT was more evident in proximal than in distal intestine, and it appeared to involve carrier-mediated absorption rather than active transport.…”

“…A role for NT in the regulation of BA cycling would be a logical extension of these findings. Support for the notion that NT relates to BA function derives from our finding that intestinal NT mRNA expression and blood levels of NT are acutely affected by altering intestinal BA concentration during feeding and by changing the distribution of the BA pool in models of cholestasis and biliary diversion (26). Also consistent is the pharmacological similarity between NT and cholescystokinin, which includes effects on pancreatic secretion, gall bladder contractility, gut motility, anorexia, and neuroleptic activity (4,7).…”

“…Not only is there controversy regarding the primary site (41) and the mechanism (2, 58) of conjugated BA absorption, but there is uncertainty as to whether hormonal factors control this process (31). However, our recent studies in the rat (25,26) argue that neurotensin (NT), a peptide stored in mucosal enteroendocrine cells (60) and released by the ingestion of fat (21,22), is a strong candidate regulator of intestinal BA uptake. It is well accepted that NT operates hormonally to optimize the digestion of fat by slowing the movement of chyme (28) and stimulating pancreatic enzyme secretion (3).…”

Molecular characterization of structure and tissue distribution of chicken neurotensin receptor

“…NT has multiple functions as a neurotransmitter and as a circulating hormone. In the gastrointestinal (GI) tract, NT is involved in regulation of gastric and intestinal motility [1,38], gastric, pancreatic and biliary secretion [18,42], mucosal growth [12,15,21,43], and inflammatory response [4,16]. These functions of NT are mediated by an NT receptor (NTR).…”