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.

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

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.

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.

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.

Melatonin inhibits alcohol-induced increases in duodenal mucosal permeability in rats in vivo

2013 ◽  
Vol 305 (1) ◽  
pp. G95-G105 ◽  
Author(s):  
Anna Sommansson ◽  
Wan Salman Wan Saudi ◽  
Olof Nylander ◽  
Markus Sjöblom
Keyword(s):  
Nicotinic Receptor ◽  
Mucosal Injury ◽  
Paracellular Permeability ◽  
Ethanol Exposure ◽  
Mucosal Permeability ◽  
Duodenal Motility ◽  
Gastrointestinal Barrier ◽  
Induced Changes ◽  
Epithelial Inflammation

Increased intestinal permeability is often associated with epithelial inflammation, leaky gut, or other pathological conditions in the gastrointestinal tract. We recently found that melatonin decreases basal duodenal mucosal permeability, suggesting a mucosal protective mode of action of this agent. The aim of the present study was to elucidate the effects of melatonin on ethanol-, wine-, and HCl-induced changes of duodenal mucosal paracellular permeability and motility. Rats were anesthetized with thiobarbiturate and a ∼30-mm segment of the proximal duodenum was perfused in situ. Effects on duodenal mucosal paracellular permeability, assessed by measuring the blood-to-lumen clearance of 51Cr-EDTA, motility, and morphology, were investigated. Perfusing the duodenal segment with ethanol (10 or 15% alcohol by volume), red wine, or HCl (25–100 mM) induced concentration-dependent increases in paracellular permeability. Luminal ethanol and wine increased, whereas HCl transiently decreased duodenal motility. Administration of melatonin significantly reduced ethanol- and wine-induced increases in permeability by a mechanism abolished by the nicotinic receptor antagonists hexamethonium (iv) or mecamylamine (luminally). Signs of mucosal injury (edema and beginning of desquamation of the epithelium) in response to ethanol exposure were seen only in a few villi, an effect that was histologically not changed by melatonin. Melatonin did not affect HCl-induced increases in mucosal permeability or decreases in motility. Our results show that melatonin reduces ethanol- and wine-induced increases in duodenal paracellular permeability partly via an enteric inhibitory nicotinic-receptor dependent neural pathway. In addition, melatonin inhibits ethanol-induced increases in duodenal motor activity. These results suggest that melatonin may serve important gastrointestinal barrier functions.

Testosterone suppresses endothelium-dependent dilation of rat middle cerebral arteries

2004 ◽  
Vol 286 (2) ◽  
pp. H552-H560 ◽  
Author(s):  
Rayna J. Gonzales ◽  
Diana N. Krause ◽  
Sue P. Duckles
Keyword(s):  
Vascular Tone ◽  
Cerebral Arteries ◽  
Cerebrovascular Reactivity ◽  
Male Rats ◽  
Intraluminal Pressure ◽  
Vascular Effects ◽  
Additional Increase ◽  
Testosterone Treatment ◽  
Cox Inhibitor ◽  
Middle Cerebral Arteries

Little is known about vascular effects of testosterone. We previously reported chronic testosterone treatment increases vascular tone in middle cerebral arteries (MCA; 300 μm diameter) of male rats. In the present study, we investigated the hypothesis that physiological levels of circulating testosterone affect endothelial factors that modulate cerebrovascular reactivity. Small branches of MCA (150 μm diameter) were isolated from orchiectomized (ORX) and testosterone-treated (ORX+T) rats. Intraluminal diameters were recorded after step changes in intraluminal pressure (20–100 Torr) in the absence or presence of NG-nitro-l-arginine-methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor; indomethacin, a cyclooxygenase (COX) inhibitor; and/or apamin and charybdotoxin (CTX); and KCa channel blockers used to inhibit endothelium-derived hyperpolarizing factors (EDHF). At intraluminal pressures ≥60 Torr, arteries from ORX+T developed greater tone compared with ORX arteries. This difference was abolished by removal of the endothelium but remained after treatment of intact arteries with indomethacin or l-NAME. In addition, testosterone treatment had no effect on cerebrovascular production of endothelin-1 or prostacyclin nor did it alter protein levels of endothelial NOS or COX-1. Endothelium removal after l-NAME/indomethacin exposure caused an additional increase in tone. Interestingly, the latter effect was smaller in arteries from ORX+T, suggesting testosterone affects endothelial vasodilators that are independent of NOS and COX. Apamin/CTX, in the presence of l-NAME/indomethacin, abolished the difference in tone between ORX and ORX+T and resulted in vessel diameters similar to those of endothelium-denuded preparations. In conclusion, testosterone may modulate vascular tone in cerebral arteries by suppressing EDHF.

Exogenous prostaglandin protects against acid-induced deep mucosal injury by stimulating alkaline secretion in rat duodenum

1989 ◽  
Vol 34 (11) ◽  
pp. 1686-1691 ◽  
Author(s):  
Felix W. Leung ◽  
Jerry C. Miller ◽  
Terry J. Reedy ◽  
Paul H. Guth
Keyword(s):  
Mucosal Injury ◽  
Rat Duodenum ◽  
Alkaline Secretion

Histamine and cAMP as possible mediators of acetylcholine-induced acid secretion

1980 ◽  
Vol 239 (4) ◽  
pp. G255-G260
Author(s):  
E. B. Ekblad
Keyword(s):  
Gastric Mucosa ◽  
Acid Secretion ◽  
Histamine Release ◽  
Transient Increase ◽  
Cyclic Monophosphate ◽  
H2 Antagonist ◽  
Alkaline Secretion ◽  
Camp And Cgmp

Data are presented in support of the role of histamine and adenosine 3',5'-cyclic monophosphate (cAMP) as mediators of acetylcholine-induced acid secretion in frog gastric mucosa. These data also support the notion that acetylcholine-induced alkaline secretion is mediated by guanosine 3',5'-cyclic monophosphate (cGMP). Tissue cAMP and cGMP and rates of acid secretion and histamine release were measured in in vitro preparations of frog gastric mucosa that had been stimulated by acetylcholine. A transient increase in each variable was observed, the sequence of transient maxima being histamine release, cGMP, cAMP, and acid secretion. Atropine, an anticholnergic agent, eliminated all four transient increases, the variables remaining at resting levels. Metiamide, a H2-antagonist, modified the changes observed after acetylcholine stimulation. The acid secretion transience was abolished and the transient increase in tissue cAMP was greatly diminished, whereas the tissue of cGMP transience and histamine release transience remained unchanged. A model is proposed in which acetylcholine initiates two different processes, acid and alkaline secretions.

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