Inhibition Of Intestinal Motility Research Articles

Fat-induced ileal brake in the dog depends on peptide YY

BACKGROUND & AIMS: Fat in the distal gut inhibits transit through the proximal small intestine as the ileal brake. Although the mediator of this response is not established, peptide YY (PYY) has been considered the most likely peptide candidate because inhibition of intestinal motility by fat in the distal gut correlated with the release of PYY but not other distal gut peptides such as enteroglucagon or neurotensin. Although intravenous administration of PYY inhibits intestinal transit, the role of this peptide remains to be confirmed because systemic PYY may not exert its effect by the same regulatory pathway as fat-induced ileal brake. The aim of this study was to definitively test the hypothesis that PYY mediates fat-induced ileal brake using the technique of peptide immunoneutralization. METHODS: In a fistulated dog model, intestinal transit during perfusion of the distal gut with 60 mmol/L oleate (ileal brake) was examined after intravenous administration of 0.5 mg/kg of PYY antibody (anti-PYY), nonspecific immunoglobulin G (control), or 0.15 mol/L NaCl. Intestinal transit result (cumulative percent recovery of 99mTc) was normalized within each animal against the transit result of the 0.15 mol/L NaCl experiment. RESULTS: Intestinal transit accelerated with PYY immunoneutralization, increasing cumulative percent recovery from 25.9 +/- 6.2 (control) to 81.2 +/- 6.3 (anti-PYY). CONCLUSIONS: Fat-induced ileal brake depends on PYY. (Gastroenterology 1996 May;110(5):1491-5)

Effects of glycowithanolides from Withania somnifera on morphine‐induced inhibition of intestinal motility and tolerance to analgesia in mice

AbstractEffects of glycowithanolides (Ws, 10–150 mg/kg, i.p.), consisting of sitoindosides VII‐X, in combination with withaferin‐A, from Withania somnifera, in Swiss mice were evaluated on (i) morphine‐induced inhibition of gastrointestinal tract (GIT) transit and (ii) development of tolerance to morphine‐induced analgesia. Pretreatment with Ws significantly reversed the morphine (5 mg/kg, s.c.)‐induced inhibition of GIT transit at all doses. Ws (100 mg/kg, i.p., o.d., for 10 days) significantly inhibited the development of tolerance to morphine‐induced analgesia. Ws per se did not influence the intestinal motility nor did it produce any perceptible analgesic effect. The present and earlier findings with Ws suggest its potential in alleviating the adverse effects of morphine and the attendant immunodepression.

Inhibition of intestinal motility and secretion by flavonoids in mice and rats: structure-activity relationships.

Intraperitoneal administration of some flavonoids (apigenin, flavone, kaempferol, morin, myricetin, naringin and rutin; 12.5-50 mg kg-1) significantly (P < 0.05-0.01) reduced small (28-69%) and large (83-134%) intestinal transit in mice. Other flavonoids (naringenin, silibinin, silymarin and taxifolin, 100-200 mg kg-1) reduced (23-41%; P < 0.05-0.01) intestinal transit at doses of 100-200 mg kg-1 while hesperitin, catechin and phloridzin (up to 200 mg kg-1) had no effect. This effect was antagonized by yohimbine (87-96%) and phentolamine (87-91%) but not by prazosin, propranolol, atropine, hexamethonium, mepyramine, cyproheptadine and naloxone. Yohimbine (92-96%) also antagonized the inhibitory effect of flavonols (12.5-50 mg kg-1) (P < 0.05-0.01) on intraluminal accumulation of fluid and diarrhoea induced by castor oil. By contrast, verapamil potentiated the flavonol effect. It is suggested that these effects, influenced by the structure of the molecules, are mediated by alpha 2-adrenergic receptors and calcium.

Inhibition of intestinal motility and reversal of postlaparotomy ileus by selective α2-adrenergic drugs in the rat

Background: The effects of selective α-agonist medetomidine and α2-antagonist atipamezole on gastrointestinal motility were studied. Methods: The passage of intragastrically administered Evans blue in the small bowel of unanesthetized rats was followed, and the stomachs were weighted after killing the rats. Results: Subcutaneous medetomidine, 0.01–0.1 mg/kg, was found to delay small intestinal transit but not gastric emptying, with a maximal effect seen at 0.03 mg/kg. Atipamezole fully reversed the effect of 0.1 mg/kg of medetomidine with a dose of 2.5 mg/kg. Atipamezole alone did not affect small intestinal transit. Subcutaneous morphine, 6 mg/kg, delayed gastric emptying and small intestinal transit, whereas intraperitoneal morphine only delayed gastric emptying. Subcutaneous atipamezole, 0.06 mg/kg, was partially able to reverse the delayed intestinal transit but did not inhibit morphine-induced gastric retention. Subcutaneous atipamezole, 0.06 mg/kg, reversed laparotomy-induced ileus completely. Conclusions: Atipamezole may provide a useful treatment for postlaparotomy ileus.

Demonstration of antidiarrheal and antimotility effects of wood creosote.

Wood creosote administered to rats prevented castor-oil-induced diarrhea with an ED50 of 53 mg/kg p.o. This antidiarrheal effect was apparently produced by acceleration of net fluid absorption from the intestine, as shown by a 52% decrease (p < 0.001) of residual fluid volume in an intestinal loop, and partly by suppression of intestinal motility. Wood creosote also inhibited spontaneous longitudinal contractions of isolated ileal segments in rats (IC50 = 28 mg/l) and guinea pigs (IC50 = 17 mg/l). Contractions of the guinea pig ileum induced by electrical stimulation, bradykinin and acetylcholine were also inhibited dose-dependently. We conclude that wood creosote has an antidiarrheal activity and that this effect is exerted by inhibition of intestinal motility and by augmentation of net fluid absorption from the intestine.

In vitro inhibition of intestinal motility by phenylethanolaminotetralines: evidence of atypical β‐adrenoceptors in rat colon

1. The new compounds phenylethanolaminotetralines (PEAT), unlike the reference beta-adrenoceptor agonists isoprenaline (Iso), ritodrine (Ri) and salbutamol (Sal), produced half-maximal inhibition of spontaneous motility of rat isolated proximal colon at substantially lower concentrations (EC50 2.7-30 nM) than those inducing beta 2-adrenoceptor-mediated responses (relaxation of guinea-pig isolated trachea and rat uterus) and had virtually no chronotropic action (EC50 greater than 3 x 10(5) M) on the guinea-pig isolated atrium (a beta 1-adrenoceptor-mediated response). 2. The nonselective beta-adrenoceptor antagonists alprenolol and propranolol prevented the inhibition of rat colon motility by the PEAT with low and different potencies (pA2 values around 7.5 and 6.5 respectively). Conversely alprenolol and propranolol had a higher and similar potency (pA2 values around 9.0) in preventing typical beta 1 or beta 2-responses (increase in atrial frequency by Iso or tracheal relaxation by Ri or Sal). 3. The selective beta-adrenoceptor antagonists CGP 20712A (beta 1) and ICI 118,551 (beta 2) either alone or in combination, did not prevent rat colon motility inhibition by the representative PEAT SR 58611A, which was also fully resistant to alpha-adrenoceptor, acetylcholine, dopamine, histamine, opioid and 5-hydroxytryptamine antagonists. 4. These results indicate that the PEAT are a new class of beta-adrenoceptor agonists and suggest that their preferential intestinal action may be accounted for by selectivity for atypical beta-adrenoceptors, abundant in the rat colon and distinct from the currently recognized beta 1 and beta 2 subtypes.

Pharmacological characterization of muscarinic receptors involved in McN‐A‐343‐induced effects on intestinal motility and heart rate in conscious dogs

1. Intravenous injection of the muscarinic agonist, McN-A-343, in conscious dogs equipped with an ileal Thiry fistula produced a dose-related inhibition of intestinal phasic contractile activity, and an increase in heart rate. 2. The inhibitory action of McN-A-343 on motility was antagonized with different potencies by antimuscarinic drugs. The non-selective drug, N-methylatropine, blocked the McN-A-343 effect as well as the reflex phasic activity. The M1-selective compound, pirenzepine (1-30 micrograms kg-1), was a potent antagonist of the McN-A-343 effect, whereas the cardioselective M2-antagonist, AF-DX 116, and the smooth muscle selective compound, 4-diphenylacetoxy-N-methyl piperidine (4-DAMP), were completely ineffective at the doses tested. 3. The McN-A-343-induced inhibition of intestinal motility was blocked by locally applied lignocaine, suggesting the involvement of a neural inhibitory pathway. The resistance to hexamethonium and (alpha 1-, alpha 2- and beta-) adrenoceptor blocking drugs excluded transmission through a nicotinic synapse or release of catecholamines. 4. McN-A-343-induced tachycardia was also the result of muscarinic receptor activation. It was very sensitive to antagonism by 4-DAMP, while being completely unaffected by AF-DX 116. Pirenzepine displayed an intermediate profile, reducing tachycardia at doses fully active in reversing the agonist-mediated effect on intestinal motility. Propranolol partially reduced McN-A-343 tachycardia, suggesting catecholamine release. 5. The two McN-A-343 effects investigated in the present study appear to be mediated by different muscarinic receptor subtypes. While the inhibitory action on intestinal motility results from stimulation of Ml-muscarinic receptors, the tachycardia is mediated by receptors blocked selectively by 4-DAMP.

Centrally and peripherally mediated inhibition of intestinal motility by opioids.

Intracerebroventricularly injected morphine is 50-fold more potent in arresting intestinal peristalsis in rats, mice or guinea pigs than morphine administered systemically. Using quaternary naloxone as narcotic antagonist, it has been demonstrated that the peripheral pathway of the centrally mediated constipatory effect of morphine does not involve opioid peptidergic mechanisms. Further, this effect is not due to the release of opioid peptides from the pituitary, since hypophysectomy fails to affect the antipropulsive activity of morphine. On the other hand, the intestinal motility can be affected directly by activation of opiate receptors located in the gut. This was best demonstrated with loperamide, which exhibits predominantly a peripheral site of action. Thus, two mechanisms of the action of morphine on gastrointestinal propulsive activity have been demonstrated. One arises in the central nervous system (CNS) and is mediated peripherally not by opioid peptidergic pathways, whereas the other is due to a direct action of morphine on the gut.

Sympathetic nerve activity during reflex spinal inhibition of intestinal motility.

Sympathetic nerve activity during reflex spinal inhibition of intestinal motility.

Autonomic inhibition of intestinal motility in dogs associated with intra-abdominal injury.

Autonomic inhibition of intestinal motility in dogs associated with intra-abdominal injury.

Inhibition of Intestinal Motility in Man by Glucagon Given Intraportally

Inhibition of Intestinal Motility in Man by Glucagon Given Intraportally

Ether麻醉による腸運動靜止の機序について

Ether麻醉による腸運動靜止の機序について