The peptide hormone xenin induces gallbladder contractions in conscious dogs

Abstract

Xenin is a 25-amino acid peptide isolated from human gastric mucosa. The biological activities of xenin include modulating intestinal motility and affecting exocrine pancreatic secretion and gastric acid secretion. The physiological effect of xenin on the gastrointestinal tract, however, is incomplete. The objective of this study is to investigate the effects of xenin on the gastrointestinal tract motility of conscious dogs. Gastrointestinal tract and gallbladder contractions were monitored by chronically implanted force transducers. Synthetic xenin was injected intravenously during the interdigestive state with or without pretreatment with cholinergic blockers. The effects of xenin following cholecystectomy and truncal vagotomy were also investigated. Xenin induced gallbladder and jejunal contractions, although a dose-dependent response was shown only with gallbladder contractions. These effects were inhibited by pretreatment with cholinergic blockers, but were not enhanced by truncal vagotomy. The jejunal contractions were completely inhibited by cholecystectomy. The only direct effect of xenin in terms of gastrointestinal motility was to induce gallbladder contractions in conscious dogs. The neural pathway mediating xenin's action was cholinergic, but not the vagal. This novel finding indicates a new role of xenin.

Xenin-25 delays gastric emptying and reduces postprandial glucose levels in humans with and without Type 2 diabetes

“…Thus effects of Xen on insulin release may be independent of the central nervous system. Consistent with this hypothesis, effects of Xen on gall bladder contractions are inhibited by atropine, but not vagotomy (23).…”

“…In animals, Xen delays gastric emptying (25), reduces food intake (2,10,27), increases gut motility (17), augments gall bladder contractions (23), and enhances secretion from the exocrine pancreas (16). Many of these Xen effects are known to be mediated by neurons (9,10,23,25,27). In vivo mouse studies from our (54) and another (30) laboratory demonstrated that Xen increases the effects of GIP on insulin release.…”

“…Genetic and pharmacological data indicate that effects of Xen are mediated by neurotensin receptor-1 [NTSR1 (19,24,35,57)]. In animals, Xen delays gastric emptying (25), reduces food intake (2,10,27), increases gut motility (17), augments gall bladder contractions (23), and enhances secretion from the exocrine pancreas (16). Many of these Xen effects are known to be mediated by neurons (9,10,23,25,27).…”

Evaluation of the degradation and metabolic effects of the gut peptide xenin on insulin secretion, glycaemic control and satiety

“…Early studies identified a contraction and relaxation effect of xenin in the jejunum, and a relaxation effect in the colon of guinea pigs . Subsequent studies have shown xenin to elicit dose-dependent contractions in dog gall bladder and non-dose-dependent contractions in the jejunum (Kamiyama et al 2007). …”

The effect of growth hormone releasing peptide-2 on upper gastrointestinal contractile activity and food intake in conscious dogs

“…The fact that GHRP-2 inhibited postprandial upper gastrointestinal contractions in dogs with vagotomy without increasing food intake suggests that the motor inhibitory effect of GHRP-2 on the upper gastrointestinal tract is not linked to food intake. We did not verify the completeness of vagotomy, because surgical abdominal vagotomy is a very well established method and often performed in dogs to study the role of the vagal nerve [29,30]. When antagonists are used to see if they reverse the effect induced by an agent, it is important to confirm that administration of those antagonists did not alter basal motor activity.…”