Elevation of intraluminal pressure and cyclooxygenase inhibitors increases duodenal alkaline secretion

1994 ◽  
Vol 266 (1) ◽  
pp. G22-G30 ◽  
Author(s):  
M. Sababi ◽  
O. Nylander
Keyword(s):  
Hydrostatic Pressure ◽  
Receptor Antagonist ◽  
Carotid Arteries ◽  
Neural Mechanism ◽  
Transient Increase ◽  
Intraluminal Pressure ◽  
Cyclooxygenase Inhibitors ◽  
Mucosal Permeability ◽  
Duodenal Motility ◽  
Alkaline Secretion

Our aim was to study the effects of intraluminal hydrostatic pressure on duodenal mucosal alkaline secretion (DMAS) and permeability in anesthetized rats. A segment of proximal duodenum was perfused with saline and the rate of DMAS determined by backtitration. Mucosal permeability was assessed by measuring the clearance of 51Cr-EDTA (ED-C1) from blood to lumen. Raising the intraluminal hydrostatic pressure 6 mmHg above basal for 40 min induced a 75% increase in DMAS and a transient increase in ED-C1. This stimulation of DMAS was not affected by pretreatment with the muscarinergic receptor antagonist atropine (0.5 mg/kg i.v.), or the opioid receptor antagonist naloxone (15 micrograms/kg i.v.) but was strongly reduced by stripping the nerves around the carotid arteries and abolished by the ganglion blocker hexamethonium (10 mg/kg i.v.). When the distension was prolonged to 90 min, the net increase in DMAS decreased with time, indicating an adaptive mechanism. The cyclooxygenase inhibitors indomethacin (5 mg/kg i.v.) and meclofenamate (5 mg/kg i.v.) induced intermittent elevations of intraluminal pressure and increased DMAS by > 100%. This was associated with a transient increase in ED-C1. Indomethacin increased DMAS in a dose-related fashion, and the rise in both intraluminal pressure and DMAS was abolished by hexamethonium but not affected by stripping the nerves around the carotid arteries. Elevation of intraluminal pressure did not augment the rise in DMAS induced by indomethacin. It is concluded that luminal distension and cyclooxygenase inhibition increase DMAS by a similar, but not identical, neural mechanism involving nicotinergic receptors. It is speculated that the indomethacin-induced rise in DMAS is mediated via induction of duodenal motility

COX inhibition excites enteric nerves that affect motility, alkaline secretion, and permeability in rat duodenum

2001 ◽  
Vol 281 (5) ◽  
pp. G1169-G1178 ◽  
Author(s):  
Olof Nylander ◽  
Anneli Hällgren ◽  
Manaf Sababi
Keyword(s):  
Paracellular Permeability ◽  
Transient Increase ◽  
Intraluminal Pressure ◽  
Motility Pattern ◽  
Duodenal Motility ◽  
Cox Inhibitor ◽  
Enteric Nerves ◽  
Rat Duodenum ◽  
Alkaline Secretion ◽  
Low Amplitude

In anesthetized rats, the cyclooxygenase (COX) inhibitor indomethacin induces duodenal motility, increases duodenal mucosal alkaline secretion (DMAS), and evokes a transient increase in duodenal paracellular permeability (DPP). To examine whether enteric nerves influence these responses, the duodenum was perfused with lidocaine. Motility was assessed by measuring intraluminal pressure, and DPP was determined as blood-to-lumen clearance of 51Cr-EDTA. DMAS was assessed by titration. In control animals, few contractions occurred during saline perfusion and lidocaine did not alter this condition. Perfusion with 0.03–0.1% lidocaine did not affect DMAS or DPP whereas 0.3–1% lidocaine reduced DMAS and increased DPP. Indomethacin induced motility and doubled DMAS. Application of 0.03% lidocaine on the duodenal serosa reduced motility and DMAS whereas 0.03% lidocaine applied luminally inhibited DMAS only. Higher concentrations of lidocaine abolished the increase in DMAS and changed the motility pattern to numerous low-amplitude contractions, the latter effect being blocked by iloprost. The lidocaine-induced increases in DPP were markedly higher than in controls. We conclude that indomethacin activates enteric nerves that induce motility, increase DMAS, and decrease DPP.

Interaction between prostanoids, NO, and VIP in modulation of duodenal alkaline secretion and motility

1996 ◽  
Vol 271 (4) ◽  
pp. G582-G590 ◽  
Author(s):  
M. Sababi ◽  
A. Hallgren ◽  
O. Nylander
Keyword(s):  
Smooth Muscle ◽  
Methyl Ester ◽  
Inhibitory Action ◽  
Muscle Relaxation ◽  
Intraluminal Pressure ◽  
Smooth Muscle Relaxation ◽  
Pressure Measurements ◽  
Stimulatory Action ◽  
Duodenal Motility ◽  
Alkaline Secretion

The relation between duodenal motility and duodenal mucosal alkaline secretion (DMAS) was examined in anesthetized rats. The duodenum was perfused with saline, and DMAS was determined by titration. Duodenal motility, assessed by intraluminal pressure measurements, was induced by indomethacin and/or N omega-nitro-L-arginine methyl ester (L-NAME) and inhibited by iloprost or vasoactive intestinal peptide (VIP). Six of 66 rats showed spontaneous duodenal contractions. Basal DMAS was higher in these rats than in those without contractions. Rats treated with indomethacin and L-NAME before abdominal operation exhibited duodenal motility postoperatively and had higher DMAS than in controls. Iloprost abolished both the duodenal motility increase and increase in DMAS induced by indomethacin. L-NAME-induced motility and increase in DMAS were antagonized by L-arginine. VIP increased DMAS without affecting motility. VIP abolished indomethacin-induced motility and augmented indomethacin-stimulated DMAS. VIP reduced L-NAME-induced motility and slightly increased L-NAME-stimulated DMAS. It is concluded that DMAS varies with duodenal motility. Prostaglandins and NO inhibit duodenal motility, thereby indirectly reducing DMAS. VIP may have dual effects on DMAS, an inhibitory action mediated via smooth muscle relaxation and a stimulatory action independent of motility.

Effects of nitric oxide inhibition on duodenal function in rat: involvement of neural mechanisms

1995 ◽  
Vol 269 (2) ◽  
pp. G246-G254 ◽  
Author(s):  
A. Hallgren ◽  
G. Flemstrom ◽  
M. Sababi ◽  
O. Nylander
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Nicotinic Receptor ◽  
Neural Mechanism ◽  
Fluid Secretion ◽  
Bicarbonate Secretion ◽  
Mucosal Permeability ◽  
Nitric Oxide Synthase Inhibitor ◽  
Duodenal Motility ◽  
Oxide Synthase

This study examines the integrative response of several duodenal functions to nitric oxide synthase inhibition. Effects of the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) were studied in anesthetized rats, using in situ duodenal perfusion. L-NAME increased bicarbonate secretion, permeability, and fluid secretion and induced motility. Injection of L-arginine abolished L-NAME-induced motility and lowered the secretion of bicarbonate and fluid. Pretreatment with the nicotinic receptor antagonist hexamethonium prevented the rise in bicarbonate secretion and motility in response to L-NAME but did not affect the increase in mucosal permeability. Atropine diminished the L-NAME-induced increases in permeability, motility, and fluid secretion. The adrenolytic drug guanethidine did not alter the responses to the inhibitor. These results suggest that nitric oxide inhibits duodenal motility and bicarbonate secretion by suppressing a stimulatory, nicotinic receptor-dependent, neural mechanism. The L-NAME-induced contractions involve both a cholinergic, atropine-sensitive pathway and nonadrenergic, noncholinergic neural transmission. Muscarinic receptors also mediate part of the L-NAME-induced increases in mucosal permeability and fluid secretion.

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

1998 ◽  
Vol 275 (1) ◽  
pp. G95-G103 ◽  
Author(s):  
Anneli Hällgren ◽  
Gunnar Flemström ◽  
Olof Nylander
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Secretory Response ◽  
Intraluminal Pressure ◽  
Neurokinin A ◽  
Bicarbonate Secretion ◽  
Mucosal Permeability ◽  
Duodenal Motility ◽  
Enteric Nerves ◽  
Luminal Perfusion

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.

Serotonin stimulates endotoxin translocation via 5-HT3 receptors in the rat ileum

2003 ◽  
Vol 284 (5) ◽  
pp. G782-G788 ◽  
Author(s):  
Tadanori Yamada ◽  
Akio Inui ◽  
Naoki Hayashi ◽  
Masaki Fujimura ◽  
Mineko Fujimiya
Keyword(s):  
Receptor Antagonist ◽  
Jugular Vein ◽  
Ex Vivo ◽  
Intraluminal Pressure ◽  
Intestinal Lumen ◽  
Receptor Subtypes ◽  
Mucosal Permeability ◽  
Rat Ileum ◽  
Endotoxin Translocation ◽  
Ec Cells

Because few previous studies have investigated the mechanisms of endotoxin translocation induced by intestinal obstruction, we aimed to clarify whether or not serotonin [5-hydroxytryptamine (5-HT)], which is released from enterochromaffin (EC) cells, is responsible for alterations of the mucosal permeability to endotoxin and to identify the 5-HT receptor subtypes that mediate this action. FITC-labeled LPS (FITC-LPS) was injected into the ileum of rats, and the FITC-LPS level in the superior mesenteric vein was subsequently measured by using a fluorescence spectrophotometer. To measure the 5-HT release induced by high intraluminal pressure, ex vivo preparation of vascularly and luminally perfused rat ileum was used. Results demonstrated that elevated intraluminal pressure stimulates the translocation of FITC-LPS and the release of 5-HT from the EC cells into the intestinal lumen but not into the portal circulation. This FITC-LPS translocation, which was stimulated by exogenously applied 5-HT in the lumen and the jugular vein, was inhibited by 5-HT3 receptor antagonist administration both intaluminally and intravenously. The stimulatory effect of elevated intraluminal pressure on the translocation of FITC-LPS was inhibited by the intraluminal and intravenous administration of 5-HT3receptor antagonist. These results suggest that 5-HT released from EC cells may be involved in the translocation of FITC-LPS induced by elevated intraluminal pressure and that this effect is mediated by 5-HT3 receptors that may be located in the intestinal epithelium.

receptor antagonist Bosentan inhibits neointimal development in collared carotid arteries of rabbits

Life Sciences ◽  
1998 ◽  
Vol 63 (18) ◽  
pp. PL259-PL266 ◽  
Author(s):  
Giuseppe Marano ◽  
Sergio Palazzesi ◽  
Paola Bernucci ◽  
Mauro Grigioni ◽  
Roberto Formigari ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Carotid Arteries

Relation between duodenal alkaline secretion and motility in fasted and sham-fed dogs

1986 ◽  
Vol 251 (5) ◽  
pp. G591-G596 ◽  
Author(s):  
S. J. Konturek ◽  
P. Thor
Keyword(s):  
Motor Activity ◽  
Vagal Stimulation ◽  
Secretory Activity ◽  
Phase Iii ◽  
Plasma Gastrin ◽  
Marked Rise ◽  
Sham Feeding ◽  
Duodenal Motility ◽  
Alkaline Secretion ◽  
Stimulation Of

A relation between duodenal myoelectric and motor activity and alkaline secretion has been investigated in conscious dogs under basal conditions and following vagal excitation with and without pretreatment with atropine or indomethacin. It was found that duodenal alkaline secretion shows typical periodicity in phase with the myoelectric or motor activity of the duodenum, reaching a peak during phase III and a nadir during phase I of the migrating motor complex (MMC). Sham feeding interrupted the motor and secretory MMC cycle and caused a prolonged increase in duodenal myoelectric or motor activity as well as a sudden and marked rise in duodenal alkaline secretion accompanied by a significant elevation in plasma gastrin and pancreatic polypeptide. Atropine and indomethacin abolished the motor and secretory duodenal cycles and reduced basal alkaline secretion significantly. Atropine abolished, whereas indomethacin increased duodenal myoelectric or motor activity during basal conditions and after vagal stimulation. Neither atropine nor indomethacin abolished sham feeding-induced duodenal alkaline secretion. We conclude that duodenal alkaline secretion fluctuates cyclically in phase with duodenal motility, vagal excitation results in a potent stimulation of duodenal motor and secretory activity, and the mechanism of vagally induced duodenal alkaline secretion is only partly cholinergic and does not involve endogenous generation of prostaglandins.

Stimulation of growth of a colon cancer cell line by gastrin

1986 ◽  
Vol 251 (5) ◽  
pp. G597-G601 ◽  
Author(s):  
C. J. Kusyk ◽  
N. O. McNiel ◽  
L. R. Johnson
Keyword(s):  
Motor Activity ◽  
Cancer Cell Line ◽  
Secretory Activity ◽  
Colon Cancer Cell Line ◽  
Phase Iii ◽  
Marked Rise ◽  
Sham Feeding ◽  
Duodenal Motility ◽  
Alkaline Secretion ◽  
Stimulation Of

A relation between duodenal myoelectric and motor activity and alkaline secretion has been investigated in conscious dogs under basal conditions and following vagal excitation with and without pretreatment with atropine or indomethacin. It was found that duodenal alkaline secretion shows typical periodicity in phase with the myoelectric or motor activity of the duodenum, reaching a peak during phase III and a nadir during phase I of the migrating motor complex (MMC). Sham feeding interrupted the motor and secretory MMC cycle and caused a prolonged increase in duodenal myoelectric or motor activity as well as a sudden and marked rise in duodenal alkaline secretion accompanied by a significant elevation in plasma gastrin and pancreatic polypeptide. Atropine and indomethacin abolished the motor and secretory duodenal cycles and reduced basal alkaline secretion significantly. Atropine abolished, whereas indomethacin increased duodenal myoelectric or motor activity during basal conditions and after vagal stimulation. Neither atropine nor indomethacin abolished sham feeding-induced duodenal alkaline secretion. We conclude that duodenal alkaline secretion fluctuates cyclically in phase with duodenal motility, vagal excitation results in a potent stimulation of duodenal motor and secretory activity, and the mechanism of vagally induced duodenal alkaline secretion is only partly cholinergic and does not involve endogenous generation of prostaglandins.

Intestinal filtration-secretion due to increased intraluminal pressure in rabbits

1982 ◽  
Vol 242 (1) ◽  
pp. G65-G75
Author(s):  
E. A. Swabb ◽  
R. A. Hynes ◽  
W. G. Marnane ◽  
J. S. McNeil ◽  
R. A. Decker ◽  
...  
Keyword(s):  
Hydrostatic Pressure ◽  
Surface Area ◽  
Intestinal Transport ◽  
Blood Flow Rate ◽  
Intraluminal Pressure ◽  
Rabbit Ileum ◽  
Venous Dilatation ◽  
Small Intestinal

The mechanism of changes in small intestinal transport due to acutely increased intraluminal hydrostatic pressure (IHP) was investigated in detail using perfused in vivo rabbit intestinal segments. IHP affected passive transport in vivo by increasing effective mucosal surface area in the small intestine (indicated by 3HOH transport and tissue architectural changes) and increasing small intestinal permeability (indicated by a proportionately greater increase in mannitol than erythritol secretory clearance). IHP did not alter ileal blood flow rate measured by radioactive microspheres, despite grossly evident venous dilatation, or active intestinal transport in the ileum as measured by a) in vitro ion transport in the absence of elevated hydrostatic pressure, b) mucosal adenylate cyclase or Na-K-ATPase activities, and c) glucose-stimulated water and electrolyte absorption. Acutely increased IHP appears to influence the hydrodynamics of the mucosal microcirculation in the rabbit ileum to produce a driving force for passive filtration-secretion, which is associated with and possibly augmented by increased tissue permeability and effective surface area.

scholarly journals Endogenous opioids in the nucleus accumbens promote approach to high-fat food in the absence of caloric need

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Kevin Caref ◽  
Saleem M Nicola
Keyword(s):  
Nucleus Accumbens ◽  
Receptor Antagonist ◽  
Neural Control ◽  
Neural Mechanism ◽  
Endogenous Opioids ◽  
Neuronal Firing ◽  
Palatable Food ◽  
Sugar Consumption ◽  
High Fat ◽  
The Brain

When relatively sated, people (and rodents) are still easily tempted to consume calorie-dense foods, particularly those containing fat and sugar. Consumption of such foods while calorically replete likely contributes to obesity. The nucleus accumbens (NAc) opioid system has long been viewed as a critical substrate for this behavior, mainly via contributions to the neural control of consumption and palatability. Here, we test the hypothesis that endogenous NAc opioids also promote appetitive approach to calorie-dense food in states of relatively high satiety. We simultaneously recorded NAc neuronal firing and infused a µ-opioid receptor antagonist into the NAc while rats performed a cued approach task in which appetitive and consummatory phases were well separated. The results reveal elements of a neural mechanism by which NAc opioids promote approach to high-fat food despite the lack of caloric need, demonstrating a potential means by which the brain is biased towards overconsumption of palatable food.

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