Limits...
Neuropeptide S reduces duodenal bicarbonate secretion and ethanol-induced increases in duodenal motility in rats

View Article: PubMed Central - PubMed

ABSTRACT

Alcohol disrupts the intestinal mucosal barrier by inducing metabolic and functional changes in epithelial cells. Recently, we showed that neuropeptide S (NPS) decreases duodenal motility and increases mucosal paracellular permeability, suggesting a role of NPS in the pathogenesis of disorders and dysfunctions in the small intestine. The aim of the present study was to investigate the effects of NPS on ethanol- and HCl-induced changes of duodenal mucosal barrier function and motility. Rats were anaesthetized with thiobarbiturate, and a 30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ. The effects on duodenal bicarbonate secretion, the blood-to-lumen clearance of 51Cr-EDTA, motility and transepithelial net fluid flux were investigated. Intravenous (i.v.) administration of NPS significantly reduced duodenal mucosal bicarbonate secretion and stimulated mucosal transepithelial fluid absorption, mechanisms dependent on nitrergic signaling. NPS dose-dependently reduced ethanol-induced increases in duodenal motility. NPS (83 pmol·kg-1·min-1, i.v.) reduced the bicarbonate and fluid secretory response to luminal ethanol, whereas a 10-fold higher dose stimulated fluid secretion but did not influence bicarbonate secretion. In NPS-treated animals, duodenal perfusion of acid (pH 3) induced greater bicarbonate secretory rates than in controls. Pre-treating animals with Nω-nitro-L-arginine methyl ester (L-NAME) inhibited the effect of NPS on bicarbonate secretion. In response to luminal acid, NPS-treated animals had significantly higher paracellular permeability compared to controls, an effect that was abolished by L-NAME. Our findings demonstrate that NPS reduces basal and ethanol-induced increases in duodenal motility. In addition, NPS increases luminal alkalinization and mucosal permeability in response to luminal acid via mechanisms that are dependent on nitric oxide signaling. The data support a role for NPS in neurohumoral regulation of duodenal mucosal barrier function and motility.

No MeSH data available.


Co-administration of luminal hydrochloric acid 1.0 mM (pH 3) with intravenous NPS increases duodenal bicarbonate secretion and mucosal paracellular permeability in a NO-activity-dependent manner.A) Luminal HCl pH 3 alone had no effect, but co-administration with NPS continuous i.v. infusion 83 pmol·kg-1·min-1 significantly increased duodenal bicarbonate secretion and B) inhibited the duodenal mucosal paracellular permeability reduction except in animals pretreated with L-NAME. C) No significant changes were observed in duodenal motility. D) NPS had no effect on HCl-induced net fluid absorption. Pretreatment with L-NAME stimulated net fluid secretion. # indicates a significant (P<0.05) difference compared with baseline (0–30 min) in the same group. * indicates significantly (P<0.05) higher than the other groups.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5383292&req=5

pone.0175312.g004: Co-administration of luminal hydrochloric acid 1.0 mM (pH 3) with intravenous NPS increases duodenal bicarbonate secretion and mucosal paracellular permeability in a NO-activity-dependent manner.A) Luminal HCl pH 3 alone had no effect, but co-administration with NPS continuous i.v. infusion 83 pmol·kg-1·min-1 significantly increased duodenal bicarbonate secretion and B) inhibited the duodenal mucosal paracellular permeability reduction except in animals pretreated with L-NAME. C) No significant changes were observed in duodenal motility. D) NPS had no effect on HCl-induced net fluid absorption. Pretreatment with L-NAME stimulated net fluid secretion. # indicates a significant (P<0.05) difference compared with baseline (0–30 min) in the same group. * indicates significantly (P<0.05) higher than the other groups.

Mentions: Perfusing the duodenal lumen for 30 min with hydrochloric acid at a pH of 3 did not change the duodenal bicarbonate secretory rate or the mucosal paracellular permeability, similarly to what has been reported previously [23]. In addition, in the present study we show that duodenal motility also remained unchanged in response to a 30 min perfusion of hydrochloric acid (pH 3) (n = 7, Fig 4C). Intravenous NPS at 83 pmol·kg-1·min-1 (n = 7) significantly increased duodenal bicarbonate secretion (p<0.05), an effect that was abolished by pretreatment with 0.25 mg/h i.v. L-NAME infusion (n = 5, Fig 4A). NPS also significantly increased duodenal mucosal paracellular permeability, an effect that was abolished by L-NAME (Fig 4B). Furthermore, administration of i.v. NPS during luminal acid perfusion did not change the motility response to luminal acid (p>0.05, Fig 4C). Similarly, 83 pmol·kg-1·min-1 NPS did not change the net fluid flux (p>0.05, n/N = 7/63) response to luminal acid compared to luminal acid alone (n/N = 6/54). During pretreatment with L-NAME (n/N = 6/54), acid together with NPS did not induce net fluid absorption, instead net fluid secretion was observed (Fig 4D).


Neuropeptide S reduces duodenal bicarbonate secretion and ethanol-induced increases in duodenal motility in rats
Co-administration of luminal hydrochloric acid 1.0 mM (pH 3) with intravenous NPS increases duodenal bicarbonate secretion and mucosal paracellular permeability in a NO-activity-dependent manner.A) Luminal HCl pH 3 alone had no effect, but co-administration with NPS continuous i.v. infusion 83 pmol·kg-1·min-1 significantly increased duodenal bicarbonate secretion and B) inhibited the duodenal mucosal paracellular permeability reduction except in animals pretreated with L-NAME. C) No significant changes were observed in duodenal motility. D) NPS had no effect on HCl-induced net fluid absorption. Pretreatment with L-NAME stimulated net fluid secretion. # indicates a significant (P<0.05) difference compared with baseline (0–30 min) in the same group. * indicates significantly (P<0.05) higher than the other groups.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5383292&req=5

pone.0175312.g004: Co-administration of luminal hydrochloric acid 1.0 mM (pH 3) with intravenous NPS increases duodenal bicarbonate secretion and mucosal paracellular permeability in a NO-activity-dependent manner.A) Luminal HCl pH 3 alone had no effect, but co-administration with NPS continuous i.v. infusion 83 pmol·kg-1·min-1 significantly increased duodenal bicarbonate secretion and B) inhibited the duodenal mucosal paracellular permeability reduction except in animals pretreated with L-NAME. C) No significant changes were observed in duodenal motility. D) NPS had no effect on HCl-induced net fluid absorption. Pretreatment with L-NAME stimulated net fluid secretion. # indicates a significant (P<0.05) difference compared with baseline (0–30 min) in the same group. * indicates significantly (P<0.05) higher than the other groups.
Mentions: Perfusing the duodenal lumen for 30 min with hydrochloric acid at a pH of 3 did not change the duodenal bicarbonate secretory rate or the mucosal paracellular permeability, similarly to what has been reported previously [23]. In addition, in the present study we show that duodenal motility also remained unchanged in response to a 30 min perfusion of hydrochloric acid (pH 3) (n = 7, Fig 4C). Intravenous NPS at 83 pmol·kg-1·min-1 (n = 7) significantly increased duodenal bicarbonate secretion (p<0.05), an effect that was abolished by pretreatment with 0.25 mg/h i.v. L-NAME infusion (n = 5, Fig 4A). NPS also significantly increased duodenal mucosal paracellular permeability, an effect that was abolished by L-NAME (Fig 4B). Furthermore, administration of i.v. NPS during luminal acid perfusion did not change the motility response to luminal acid (p>0.05, Fig 4C). Similarly, 83 pmol·kg-1·min-1 NPS did not change the net fluid flux (p>0.05, n/N = 7/63) response to luminal acid compared to luminal acid alone (n/N = 6/54). During pretreatment with L-NAME (n/N = 6/54), acid together with NPS did not induce net fluid absorption, instead net fluid secretion was observed (Fig 4D).

View Article: PubMed Central - PubMed

ABSTRACT

Alcohol disrupts the intestinal mucosal barrier by inducing metabolic and functional changes in epithelial cells. Recently, we showed that neuropeptide S (NPS) decreases duodenal motility and increases mucosal paracellular permeability, suggesting a role of NPS in the pathogenesis of disorders and dysfunctions in the small intestine. The aim of the present study was to investigate the effects of NPS on ethanol- and HCl-induced changes of duodenal mucosal barrier function and motility. Rats were anaesthetized with thiobarbiturate, and a 30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ. The effects on duodenal bicarbonate secretion, the blood-to-lumen clearance of 51Cr-EDTA, motility and transepithelial net fluid flux were investigated. Intravenous (i.v.) administration of NPS significantly reduced duodenal mucosal bicarbonate secretion and stimulated mucosal transepithelial fluid absorption, mechanisms dependent on nitrergic signaling. NPS dose-dependently reduced ethanol-induced increases in duodenal motility. NPS (83 pmol&middot;kg-1&middot;min-1, i.v.) reduced the bicarbonate and fluid secretory response to luminal ethanol, whereas a 10-fold higher dose stimulated fluid secretion but did not influence bicarbonate secretion. In NPS-treated animals, duodenal perfusion of acid (pH 3) induced greater bicarbonate secretory rates than in controls. Pre-treating animals with N&omega;-nitro-L-arginine methyl ester (L-NAME) inhibited the effect of NPS on bicarbonate secretion. In response to luminal acid, NPS-treated animals had significantly higher paracellular permeability compared to controls, an effect that was abolished by L-NAME. Our findings demonstrate that NPS reduces basal and ethanol-induced increases in duodenal motility. In addition, NPS increases luminal alkalinization and mucosal permeability in response to luminal acid via mechanisms that are dependent on nitric oxide signaling. The data support a role for NPS in neurohumoral regulation of duodenal mucosal barrier function and motility.

No MeSH data available.