Anneli Hällgren

Adherent surface mucus gel restricts diffusion of macromolecules in rat duodenum in vivo

The aim of this study was to investigate the permeability of the adherent mucus gel layer in rat duodenum in vivo to macromolecules applied in the lumen. Rats were anesthetized with thiobarbiturate, and the duodenum was perfused with isotonic NaCl solution containing large-molecular-size secretagogues. Effects on mucosal HCO(-)(3) secretion and blood-to-lumen (51)chromium-labeled EDTA clearance were used as indexes that compounds had migrated across the mucus layer. Exposure to a low concentration of papain (10 U/100 ml) for 30 min removed the mucus layer without damage to the epithelium and induced or markedly enhanced HCO(-)(3) secretory responses to cholera toxin (molecular mass of 85 kDa) or glucagon (3.5 kDa). Water extracts from a VacA cytotoxin (89 kDa) producing Helicobacter pylori strain, but not from a toxin-negative isogenic mutant, caused a small increase in HCO(-)(3) secretion but only after the mucus layer had been removed by papain. The duodenal surface mucus gel thus significantly restricts migration of macromolecules to the duodenal surface. Release of bacterial toxins at the cell-mucus interface may enhance or be a prerequisite for their effects on the gastrointestinal mucosa.The aim of this study was to investigate the permeability of the adherent mucus gel layer in rat duodenum in vivo to macromolecules applied in the lumen. Rats were anesthetized with thiobarbiturate, and the duodenum was perfused with isotonic NaCl solution containing large-molecular-size secretagogues. Effects on mucosal [Formula: see text]secretion and blood-to-lumen51chromium-labeled EDTA clearance were used as indexes that compounds had migrated across the mucus layer. Exposure to a low concentration of papain (10 U/100 ml) for 30 min removed the mucus layer without damage to the epithelium and induced or markedly enhanced [Formula: see text]secretory responses to cholera toxin (molecular mass of 85 kDa) or glucagon (3.5 kDa). Water extracts from a VacA cytotoxin (89 kDa) producing Helicobacter pylori strain, but not from a toxin-negative isogenic mutant, caused a small increase in[Formula: see text] secretion but only after the mucus layer had been removed by papain. The duodenal surface mucus gel thus significantly restricts migration of macromolecules to the duodenal surface. Release of bacterial toxins at the cell-mucus interface may enhance or be a prerequisite for their effects on the gastrointestinal mucosa.

Interaction between neurokinin A, VIP, prostanoids, and enteric nerves in regulation of duodenal function

Neurokinin A (NKA) induces duodenal motility and increases mucosal permeability and bicarbonate secretion in the in situ perfused duodenum in anesthetized rats. In the present study, the NKA-induced increase in mucosal permeability was potentiated by luminal perfusion with lidocaine and diminished by vasoactive intestinal peptide (VIP) but unaltered by elevated intraluminal pressure. Elevation of intraluminal pressure, however, potentiated the stimulatory effect of NKA on bicarbonate secretion. In contrast, the tachykinin decreased the rate of alkalinization in rats subjected to elevated intraluminal pressure and treated with indomethacin. Similarly, NKA partially inhibited the VIP-stimulated bicarbonate secretion. Luminal lidocaine did not affect the secretory response to NKA. The motility induced by NKA was unaffected by VIP or lidocaine but decreased by elevated intraluminal pressure. It is concluded that the NKA-induced increase in duodenal mucosal bicarbonate secretion is independent of neurons and possibly mediated by prostanoids. The increase in mucosal permeability in response to NKA may be suppressed by mucosal nerves, perhaps utilizing VIP as one of the transmitters.Neurokinin A (NKA) induces duodenal motility and increases mucosal permeability and bicarbonate secretion in the in situ perfused duodenum in anesthetized rats. In the present study, the NKA-induced increase in mucosal permeability was potentiated by luminal perfusion with lidocaine and diminished by vasoactive intestinal peptide (VIP) but unaltered by elevated intraluminal pressure. Elevation of intraluminal pressure, however, potentiated the stimulatory effect of NKA on bicarbonate secretion. In contrast, the tachykinin decreased the rate of alkalinization in rats subjected to elevated intraluminal pressure and treated with indomethacin. Similarly, NKA partially inhibited the VIP-stimulated bicarbonate secretion. Luminal lidocaine did not affect the secretory response to NKA. The motility induced by NKA was unaffected by VIP or lidocaine but decreased by elevated intraluminal pressure. It is concluded that the NKA-induced increase in duodenal mucosal bicarbonate secretion is independent of neurons and possibly mediated by prostanoids. The increase in mucosal permeability in response to NKA may be suppressed by mucosal nerves, perhaps utilizing VIP as one of the transmitters.

Exposure of the Duodenum to High Concentrations of Hydrochloric Acid: Effects on Mucosal Permeability, Alkaline Secretion, and Blood Flow

Proximal duodenum was perfused with HCl for 5 min and the effects on blood-to-lumen clearance of 51Cr-EDTA (ED-Cl), morphology, luminal alkalinization, and blood flow determined in anesthetized rats. The rate of alkalinization was determined by back titration and blood flow assessed by laser Doppler flowmetry or by ultrasonic transit time flowmetry. Perfusion of duodenum with 30, 50 or 100 mM HCl for 5 min increased ED-Cl in a concentration-dependent manner and induced a small increase in alkalinization but had no effect on blood flow. At 55 min after cessation of perfusion with 100 mM HCl ED-Cl was 2.2-fold higher than control whereas the ED-Cl values in animals perfused with 30 or 50 mM HCl were not different from pre-acid control values. 100 mM HCl also induced an increase in 14C-mannitol and 14C-polyethylene glycol 4000 clearance, suggesting that HCl does indeed increase mucosal permeability. The 100 mM HCl-induced rise in mucosal permeability most probably reflects disturbance of mucosal integrity because three of five animals exhibited villous tip damage. The increases in ED-Cl in response to 100 mM HCl were the same in control rats as in rats with the renal pedicles ligated, indicating that the acid susceptibility is not affected by acute functional nephrectomy.

Neurokinin A increases duodenal mucosal permeability, bicarbonate secretion, and fluid output in the rat

The aim of this study was to examine the integrative response to neurokinin A (NKA) on duodenal mucosal permeability, bicarbonate secretion, fluid flux, and motility in an in situ perfusion model in anesthetized rats. Intravenous infusion of NKA (100, 200, and 400 pmol.kg-1.min-1) induced duodenal motility. Furthermore, duodenal mucosal bicarbonate secretion, fluid output, and mucosal permeability increased in response to NKA. Pretreatment with the nicotinic antagonist hexamethonium did not change the response in any of the parameters investigated, whereas the NK2-receptor antagonist MEN 10,627 effectively inhibited all responses to NKA. Indomethacin induced duodenal motility and stimulated bicarbonate secretion. In indomethacin-treated rats, NKA further increased motility but decreased indomethacin-stimulated bicarbonate secretion by 70%. The NKA-induced increase in mucosal permeability was unaltered by indomethacin. It is concluded that NKA not only induces motility but also increases mucosal permeability and fluid output. Furthermore, the neuropeptide may have both stimulative and inhibitory effects on bicarbonate secretion. All responses to NKA are dependent on NK-2 receptor activation but are not mediated through nicotinic receptors.The aim of this study was to examine the integrative response to neurokinin A (NKA) on duodenal mucosal permeability, bicarbonate secretion, fluid flux, and motility in an in situ perfusion model in anesthetized rats. Intravenous infusion of NKA (100, 200, and 400 pmol ⋅ kg-1 ⋅ min-1) induced duodenal motility. Furthermore, duodenal mucosal bicarbonate secretion, fluid output, and mucosal permeability increased in response to NKA. Pretreatment with the nicotinic antagonist hexamethonium did not change the response in any of the parameters investigated, whereas the NK2-receptor antagonist MEN 10,627 effectively inhibited all responses to NKA. Indomethacin induced duodenal motility and stimulated bicarbonate secretion. In indomethacin-treated rats, NKA further increased motility but decreased indomethacin-stimulated bicarbonate secretion by 70%. The NKA-induced increase in mucosal permeability was unaltered by indomethacin. It is concluded that NKA not only induces motility but also increases mucosal permeability and fluid output. Furthermore, the neuropeptide may have both stimulative and inhibitory effects on bicarbonate secretion. All responses to NKA are dependent on NK-2 receptor activation but are not mediated through nicotinic receptors.

Duodenal Mucosal Permeability, Bicarbonate Secretion and Motility: Aspects of regulation and integration of duodenal function in the rat Minireview based on a doctoral thesis

Duodenal mucosal permeability, bicarbonate secretion and motility : aspects of regulation and integration of duodenal function in the rat