Ileal Motility Research Articles

Protective effect of a lipoxygenase inhibitor, nordihydroguaretic acid, on the ileal motor disturbances induced by Serratia marcescens endotoxin in rats.

This study was conducted to examine the effects of peptidoleukotrienes on the ileal contractility disturbances induced by Serratia marcescens endotoxin in rats. Thirty-two male Wistar rats were divided into four groups (n = 8 each). The first group was given only an anesthetic agent (control group); the second group was given the endotoxin (endotoxin group); the third group was given a lipoxygenase inhibitor, nordihydroguaretic acid (NDGA); and the fourth group was given NDGA 10 min before administration of the endotoxin (NDGA+endotoxin group). The isolated ileum response was recorded in each group. Normal contractile activity was seen in the control group. After the endotoxin was given. the isolated ileum did not respond to 497acetylcholine (ACh) in the endotoxin group, but the contractile results of isolated ileum to ACh were similar to the control group results in both the NDGA and endotoxin+NDGA groups. The results of this study demostrate that leukotrienes may play a role in endotoxin-induced ileal contractility disturbances, and that the lipoxygenase inhibitor, NDGA, could be useful for the treatment of ileal motility disturbances induced by endotoxin.

Participation of nitric oxide synthase and cyclo-oxygenase in the signal transduction pathway of ileal muscarinic acetylcholine receptors

Parasympathetic activation of ileal motility is essential for intestinal physiology. We have previously demonstrated that carbachol activates muscarinic acetylcholine receptors (mAChR) of rat intestine and stimulates ileal motility via phospholipase C. This activation induces phosphoinositide turnover and intracellular calcium mobilization. We show here that carbachol stimulation of rat ileal motility is potentiated by the nitric oxide synthase (NOS) inhibitor NG-monomethyl arginine. Thus, we confirm that carbachol increases, in a dose-dependent manner, the activity of a NOS isoform that depends on calcium–calmodulin binding. Its product, nitric oxide (NO), activates not only guanylyl cyclase, inducing cGMP synthesis, but also cyclo-oxygenase, producing prostaglandin E2. The prostanoid probably cooperates with NO to induce ileal smooth muscle relaxation.

Fusobacterium necrophorum haemolysin stimulates motility of ileal longitudinal smooth muscle of the guinea-pig.

Fusobacterium necrophorum haemolysin (0.5-3.1 mg protein/mL) dose-dependently induced contractions of the isolated ileal longitudinal smooth muscle of the guinea-pig. The haemolysin (3.1 mg protein/mL) -induced maximum contraction of 75% of the response to 60 mM K+ declined within 17 min and the muscles then demonstrated rhythmic contractions. Tetrodotoxin (3.1 x 10(-6) M) had no effect on the contraction due to the haemolysin. After incubation in Ca(2+)-free medium, the ileal response to the haemolysin was lost. Verapamil, a Ca2+ channel blocker, dose-dependently inhibited the contraction to the haemolysin. The rabbit anti-serum against F. necrophorum haemolysin inhibited the haemolysin-induced contraction of ileal muscle. The bacterial haemagglutinin and the lipopolysaccharide had no effect on the response of ileal muscle. These findings suggest that the haemolysin-induced direct stimulation of ileal motility dependant on Ca2+ influx will increase the probability of contact of F. necrophorum and ileal mucosa and could increase the chances of colonization for F. necrophorum.

Protein kinase C regulates NO-cGMP pathway in muscarinic receptor activation by HIV+-IgA.

In this work we demostrate that IgA purified from HIV infected patients recognizes a band with a molecular weight corresponding to radiolabelled ileal muscarinic acethylcholine receptors (mAChR) by immunoblotting. HIV+-IgA triggers the signals that are the consequence of mAChR stimulation in the intestine, regulating protein kinase C (PKC) and nitric oxide synthase (NOS) activity as well as 3',5'-cyclic guanosine monophosphate (cGMP) formation. On the one hand PKC activation by HIV+-IgA induces NOS inhibition and as a consequence, low amounts of NO that could improve local immunosuppression in the intestine; on the other hand HIV+-IgA stimulates cGMP production which could potentiate ileal motility and loss of water/electrolytes involved in intestinal damage in AIDS.

Tyrosine kinase regulatory action on ileal muscarinic effects of IFN-gamma.

Interferon-gamma (IFN-gamma) is a pleiotropic cytokine that has a large number of immunologic and nonimmunologic functions. We have described that IFN-gamma could activate muscarinic cholinergic receptors (mAchR) of rat intestine, stimulating ileal motility. We also observed that mAchR activation induced inhibition of cAMP levels and stimulation of cGMP formation. The objectives of our work were to clarify the signal transduction pathways involved in regulation of ileal motility through mAchR activation by IFN-gamma. Our results demonstrate that this cytokine produces an ileal cholinergic response through tyrosine kinase activity. The activation of tyrosine kinase mediates ileal contractility, phosphoinositide hydrolysis by phospholipase C, nitric oxide synthase via protein kinase C, and cGMP synthesis. The increment in ileal motility is probably due to hyperproduction of prostaglandin E2 (PGE2) by ileal tissue. This prostanoid is an important mediator because it stimulates ileal motility. We conclude that IFN-gamma not only immunomodulates the gut microenvironment but also exerts a local nonimmunologic regulation on intestinal motility.

The avian cecum: Update and motility review

The avian cecum is a blind-ended sac that extends from the proximal end of the colon. Ceca may be of several different histological types; they range in size from large and paired to very small and single, or they may be completely absent. Cecal types and sizes are summarized herein by taxonomic group. The intestinal type is best known; it may contain fluid, food particles, microorganisms, and substances produced by the ceca. Ceca may serve as the site for several different functions, especially digestion of small food particles, absorption of nutrients, production of immunoglobulins and antibodies, microbial action of beneficial and pathogenic organisms, utilization and absorption of water, and metabolism of uric acid into amino acids. Ceca in turkeys, chickens, and other galliforms have active motility that stirs and periodically evacuates the luminal contents. Contractions of the cecal wall propagate in either direction, with the majority being toward the cecal tip and most numerous when the ceca are filling with digesta. Propagation velocity of the contractions is affected by the presence or absence of food in the lumen. Cecal mixing contractions do not seem to be related to ileal motility. J. Exp. Zool. 283:441–447, 1999. © 1999 Wiley-Liss, Inc.

Altered myoelectrical activity in noninflamed ileum of rats with colitis induced by trinitrobenzene sulphonic acid.

Changes in gastric emptying and orocaecal transit time in patients with ulcerative colitis suggest that disturbances in gut motility may not be restricted to inflamed sites. This study sought to characterize changes in the motility of noninflamed ileum in a rat colitis model and to explore the mechanism(s) potentially involved. The myoelectrical activity of the ileum was recorded in rats with trinitrobenzene sulphonic acid (TNBS)-induced colitis. The degree of ileal and colonic inflammation was assessed by quantification of macroscopic damage and myeloperoxidase activity (MPO). The effect on ileal motility of pretreatment with atropine, indomethacin and NG-nitro-L-arginine-methyl ester (L-NAME) was investigated. TNBS-induced inflammation was restricted to the distal colon, as evidenced by morphological scores and MPO. Colitis was associated with increased frequency of ileal migrating motor complexes, characterized mainly by a decrease in the duration of phases I and III. The occurrence of ileal giant migrating complexes remained unchanged. The myoelectrical changes observed in the ileum persisted after treatment with atropine, indomethacin and L-NAME. Distal colitis is associated with abnormal myoelectrical activity in the noninflamed ileum of rats. Neither acetylcholine nor prostaglandins and nitric oxide seem to be involved.

Relationships between cecoileal reflux and ileal motor patterns in conscious pigs.

Ileal infusion of cecocolonic contents, used to mimick reflux, enhanced terminal ileal motility, increasing the frequencies of prolonged propagated contractions (PPC) and discrete clustered contractions (DCC). Because the reflux rate in dogs and humans is marginal, the relationship of these motor patterns to reflux remained putative. In six conscious pigs, the ileal pH, used to indicate reflux event, was measured 10 and 5 cm proximal to the ileocecal sphincter (ICS). Ileal motility was evaluated with three strain gauges 15, 10, and 5 cm proximal to the ICS. Ileal pH dips were observed about eight times per hour in the fasting or fed state, and 46% of the pH dips were preceded by a retrograde contraction. During pH dips, frequency of ileal contractions not classified as PPC or DCC was significantly increased. Of the PPC 52% occurred immediately after the start of the dip and might act as a clearance mechanism because dips associated with PPC were of smaller amplitude and duration than those not associated with PPC. Most DCC also occurred during pH dips but their delay to the onset of the dip was longer. The pig presents frequent cecoileal reflux events associated with ileal motor patterns, some of them might facilitate reflux, whereas others act as a clearance mechanism.

Intracellular Signals Coupled to Different Rat Ileal Muscarinic Receptor Subtypes

Taking into account that the activation of different subtypes of ileal muscarinic acetylcholine receptors (mAChR) regulate gut functions such as tone, motility, and electrolyte secretion, we characterized the expression of mAChR in ileal-purified membranes. We also studied intracellular signals triggered by mAChR activation. Binding parameters obtained from saturation assays with the nonselective tritiated muscarinic antagonist, quinuclidynil benzilate ([ 3H]-QNB), were maximal number of binding sites (Bmax): 30 ± 2 fmol/mg prot and dissociation constant (Kd): 0.2 ± 0.03 nM. The competitive inhibition of [ 3H]-QNB specific binding by various nonlabelled muscarinic antagonists was measured and the rank order of potency was: atropine (ATROP) > 4-DAMP > AF-DX 116 > pirenzepine (PZ). The activation of mAChR by carbachol (CARB) increased ileal motility in a concentration-dependent manner (EC 50 2 × 10 −7 M). The antagonists' order of potency to displace dose-response curve of CARB was: ATROP > 4-DAMP > AF-DX116 > PZ. Optimal concentration of CARB on ileal strips increased phosphoinositide turnover and cGMP levels by activating m 3 receptor subtype and decreased isoproterenol (ISO) stimulated levels of cAMP due to M 2 receptor activation. We can conclude that the activation of different mAchR subtypes triggers different intracellular signals that could regulate intestinal tone and motility.

Effects of Fractionated Abdominal Irradiation on Small Intestinal Motility Studies in a Novel In Vitro Animal Model

Disordered small intestinal motility occurs frequently during acute radiation enteritis. However, the characteristics and time course of the motor dysfunction are poorly defined. These parameters were assessed in a novel animal model of radiation enteritis. Ileal pressures were recorded in vitro with perfused micromanometric catheter using an arterially perfused ileal loop in 22 ferrets following fractionated abdominal irradiation (9 doses 2.50 Gy thrice weekly for 3 weeks). Tissue damage was graded histologically. Studies were performed 3 to 29 days after irradiation. Tissue from 7 control animals was also studied. All treated animals developed diarrhoea. Histology showed changes consistent with mild to moderate radiation enteritis. Following irradiation, there was an initial increase in frequency followed by a non-significant reduction in the frequency, but not the amplitude of ileal pressure waves. The frequency of pressure waves showed an inverse relationship with time after radiation (r = -0.634, p < 0.002). There was no relationship between motility and histology. We conclude that abdominal irradiation is associated with a time-dependent reduction in ileal motility which does not correlate with light microscopic changes.

Local regulation of ileal tone in healthy humans.

We previously showed that a meal induced, in the human terminal ileum, a delayed tonic relaxation, which could be related to the ileal delivery of meal residues and/or endogenous secretions released by a meal. In this study, we assessed the effects of some components of the ileal contents on its motor activity. In six healthy subjects, we studied ileal tonic and phasic motility in response to the infusion into the terminal ileum of different isotonic solutions: saline, glycochenodeoxycholic acid (GDCA), triglycerides, and short-chain fatty acids (SCFA). Tonic activity was not modified by saline, whereas it was significantly decreased by GDCA and triglycerides (maximal increase in intrabag volume 139 +/- 7% and 152 +/- 16%, respectively, P < 0.01), and significantly increased by SCFA (maximal decrease in intrabag volume 72 +/- 4%, P < 0.01). No significant change of phasic activity was evidenced with either solution. We conclude that 1) bile acids and triglycerides not absorbed in the more proximal gut could be involved in the ileal relaxation occurring after eating and 2) local stimulation of chemoreceptors is of importance in the regulation of ileal motility.

Adrenergic denervation hypersensitivity in ileal circular smooth muscle after small bowel transplantation in rats.

Effects of small bowel transplantation (SBT) on ileal motility are unknown. The aim of the present study was to investigate changes in spontaneous contractile activity and sensitivity to cholinergic and adrenergic agents in the ileal circular muscle after SBT in rats. Orthotopic SBT was performed in syngeneic rats to avoid immune phenomena. Distal ileal circular muscle strips from rats one week (N = 10) and eight weeks (N = 10) after SBT were stretched to optimal length (Lo), and basal spontaneous activity at Lo was measured. Dose-response experiments to the cholinergic agonist bethanechol (Be, 10(-8)-10(-4) M) were performed in the presence of tetrodotoxin (TTX, 10(-6) M) and to the adrenergic agonist norepinephrine (NE, 10(-8)-10(-4) M) with or without TTX. ED50 (negative log of drug-concentration that induced 50% effect) was calculated. We also studied rats with selective jejunoileal ischemia/ reperfusion, intestinal transection/reanastomosis, naive controls, and sham operated controls (N > or = 8/group). Spontaneous basal activity did not differ among groups. Sensitivity to Be was not different in rats after SBT or in other groups compared to control tissue. After SBT, hypersensitivity to NE was shown by a significant increase of ED50 at one and eight weeks after SBT (5.1 +/- 0.3 vs 6.2 +/- 0.4 and 6.2 +/- 0.2, respectively; P < 0.05) regardless of the presence of TTX. No hypersensitivity was observed after ischemia-reperfusion intestinal transection-reanastomosis, or sham operation. It is concluded that ileal hypersensitivity to NE was related to the extrinsic denervation obligated by the transplantation procedure, possibly mediated through an increase in number of receptors on smooth muscle, not on the enteric nerves.

PSYCHOSOCIAL ASPECTS OF FUNCTIONAL GASTROINTESTINAL DISORDERS

Increased numbers of psychiatric diagnoses and increased levels of psychological distress are seen in the majority of medical clinic patients with gastrointestinal motility disorders. In IBS, psychological symptoms are believed to be comorbid conditions, which do not cause the motility disorder but which do influence the patient's decision to consult a physician. In functional dyspepsia, psychological symptoms are present in many patients, but their role is not known; the available data suggest that psychological symptoms do not predict which patients will consult a physician. Among constipated patients, anxiety is believed to contribute to the development and course of pelvic floor dyssynergia by increasing pelvic floor muscle tension. Constipated patients without physiologic abnormalities to explain their constipation appear to have more psychological symptoms than those with delayed colonic transit, but there is significant psychological distress even in patients with slow transit constipation. Psychological symptoms do not seem to predict which constipated patients will consult a physician. There is an increased incidence of psychiatric diagnoses in patients with esophageal motility disorders as well, but the role that these psychological symptoms play in the course of the disorder is not known. Patients with the most common gastrointestinal motility disorders, IBS and dyspepsia, report experiencing more stressful life events, and IBS patients appear to show a greater increase in gastrointestinal symptoms when exposed to stressors. Laboratory studies document that acute psychological stressors do alter gastric, small bowel, and colonic motility, and patients with IBS appear to show a greater change in colonic and ileal motility with stress than healthy controls. Greater reactivity has not been demonstrated for the esophagus or stomach, however, and it has not been demonstrated for other gastrointestinal motility disorders. A characteristic of many patients who consult gastroenterologists for IBS and other motility disorders is a tendency to report multiple somatic complaints (including many nongastrointestinal complaints) and to overuse medical resources. This pattern of behavior is referred to as somatization or abnormal illness behavior. One source of abnormal illness behavior is childhood social learning, which occurs (1) when parents provide gifts or special privileges to a child who reports somatic symptoms or (2) when parents model abnormal illness behaviors themselves.

PYY and GLP-1 contribute to feedback inhibition from the canine ileum and colon.

To explore mechanisms whereby unabsorbed nutrients in the ileum inhibit the upper gut ("ileal brake"), we perfused the canine ileum or colon and monitored phase 3 in the duodenum. Fasting motility was recorded when the ileum or colon was perfused with 154 mM NaCl, a mixed isotonic nutrient solution (Ensure), or individual nutrients (maltose, casein hydrolysates, or sodium oleate). Blood samples were collected before and during the perfusions. The ileum was also perfused with 154 mM NaCl while peptide YY (PYY) was infused by vein. In both sets of experiments, plasma levels of PYY, neurotensin, and glucagon-like peptide-1 (GLP-1) were measured. Ileal or colonic perfusion of Ensure delayed phase 3 [migrating motor complexes (MMC)] in the duodenum, inhibited ileal motility, and increased plasma levels of PYY and GLP-1. Ileal casein and oleate and colonic casein also delayed the duodenal MMC. The MMC cycle length and plasma levels of PYY were closely correlated. Intravenous PYY prolonged the MMC cycle; an intravenous dose of 100 pmol.kg-1.h-1 of PYY mimicked the effects of ileal Ensure. These results support the hypothesis that PYY, and possibly GLP-1, participate in the ileal brake. This negative feedback loop also affects the distal small bowel. The proximal colon also triggers the feedback inhibition of gut motility (colonic brake).

Changes in enteric neural regulation of smooth muscle in a rabbit model of small intestinal inflammation

In vitro electrophysiological studies of ileal circular muscle from rabbits with ricin-induced inflammation were performed to investigate whether altered neural control or myogenic activity contributes to previously described changes in in vivo myoelectric activity. Ricin treatment increased mean slow-wave amplitude but not frequency or resting membrane potential. Prolonged electrical field stimulation evoked a hyperpolarization during the stimulus train and a depolarization on cessation of stimulation. In the presence of atropine, the depolarization was larger in ricin-treated tissue than in control tissue, showing that ileitis enhanced noncholinergic excitation. The nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester reduced the hyperpolarization in ricin-treated but not in control tissue, suggesting that inflammation increased nitric oxide-mediated inhibition. Substance P desensitization reduced noncholinergic excitation and mean slow-wave amplitude only in ricin-treated tissue, demonstrating that changes in these parameters during inflammation resulted from increased release of, or sensitivity to, tachykinins. These data suggest that acute ileitis alters tachykinin- and nitric oxide-mediated neurotransmission that may affect the normal pattern of ileal motility and/or sensory reflexes.

Characterization of the interaction between muscarinic M2 receptors and β‐adrenoceptor subtypes in guinea‐pig isolated ileum

1. Contraction of guinea-pig ileum to muscarinic agonists is mediated by M3 receptors, even though they account for only 30% of the total muscarinic receptor population. The aim of this study was to characterize the biochemical and functional effects of stimulation of the predominant M2 muscarinic receptor (70%) and to investigate the hypothesis that M2 receptors specifically oppose beta-adrenoceptor-mediated effects in the ileum. 2. In guinea-pig ileal longitudinal smooth muscle slices, isoprenaline, a non-selective beta-adrenoceptor agonist, and BRL 37344 (sodium-4-[2-[2-hydroxy-2-(3- chlorophenyl)ethylamino]propyl]-phenoxyacetate sesquihydrate), a beta 3-adrenoceptor selective agonist, increased cyclic AMP accumulation with -log EC50 values of 6.6 +/- 0.1 and 5.8 +/- 0.1 respectively. Maximal stimulation by BRL 37344 (10 microM) was 26.4 +/- 5.2% of that observed with isoprenaline (10 microM). Isoprenaline (10 microM)-stimulated cyclic AMP accumulation was significantly, but not completely, inhibited by propranolol (5 microM), with a propranolol-resistant component of 28.2 +/- 6.8% of the maximal stimulation to isoprenaline. In contrast, basal and BRL 37344 responses were resistant to this antagonist. These data provide evidence that both beta 1- and beta 3-adrenoceptors activate adenylyl cyclase in guinea-pig ileum. 3. Isoprenaline (10 microM)-stimulated cyclic AMP accumulation was inhibited (67.4 +/- 0.9%) by the muscarinic agonist (+)-cis-dioxolane (-log EC50 = 7.3 +/- 0.1). The rank order of antagonist affinities against the (+)-cis-dioxolane response was (-log KB values in parentheses): atropine (9.0 +/- 0.2)>methoctramine (7.1 +/- 0.1) >p-fluoro-hexa-hydrosilaphenidol (p-F-HHSiD; 6.5 +/- 0.2) ) pirenzepine(6.3 +/- 0.2). (+)-cis-dioxolane also significantly inhibited BRL 37344 (10 IM; 56.5 +/-2.4%) stimulated cyclic AMP accumulation. These data suggest that M2 receptors mediate inhibition of cyclic AMP accumulation in response to both beta l- and beta 3-adrenoceptor stimulation in guinea-pig ileum.4. 5-Hydroxytryptamine (5-HT), vasoactive intestinal peptide, prostaglandins E2 and E1, all at 10 micro M,significantly increased cyclic AMP accumulation. (+)-cis-Dioxolane (10 micro M) inhibited both basal and agonist-induced cyclic AMP accumulation. Thus the inhibitory effect of M2 receptor agonism does not appear to be restricted to beta-adrenoceptor-stimulated cyclic AMP accumulation.5. The potential for involvement of activation of M2 receptors on responses to beta-adrenoceptor agonists was also studied functionally. Selective M3 receptor alkylation was achieved by pretreatment of tissues with 4-DAMP mustard (40 nM), in the presence of methoctramine (1 micro M; to protect M2 receptors). After washing, tissues were pre-contracted with histamine (0.3 micro M) and relaxed with isoprenaline (0.6 micro M).Under these conditions, oxotremorine M caused concentration-dependent contractions (-log EC50 of 7.8 +/- 0.1), that were surmountably antagonized by methoctramine (1 microM) with a - log KB estimate of 7.4 +/- 0.1. Similar observations were seen versus relaxation produced by BRL 37344 (1 micro M), where the-log KB value for methoctramine was 7.8 +/- 0.2. These data suggest that M2 receptors mediate a functional inhibition of relaxant responses to isoprenaline and BRL 37344.6. These findings are consistent with beta l- and beta 3-adrenoceptors coupling to stimulation of a denylylcyclase in guinea-pig ileum; a response that is inhibited by M2 receptor stimulation. Concordantly, M2 receptor stimulation also inhibits relaxation to both beta l- and beta 3-adrenoceptor stimulation. These results implicate M2 receptors in the modulation of sympathetic control of ileal motility.

MECHANISM OF CHLORAMPHENICOL-INDUCED MODULATION OF MOUSE ILEAL MOTILITY

The effect of chloramphenicol (CAP) on the intestinal motility of mice was studied. Acute and chronic CAP treatment significantly increased the food transit time. CAP produced concentration-dependent inhibition of motility of the isolated ileum of mice. Prazosin, propranolol, atropine, ouabain and chlorpromazine all failed to modulate or counteract the CAP-induced inhibition of ileal motility. However, naloxone and hexamethonium slightly modified the inhibitory response of CAP. The inhibitory response of CAP was markedly counteracted by cystine, a guanylate cyclase inhibitor. CAP increased the activity of Ca(++)-ATPase in the ileum in all experiments. Our results suggest that the CAP-induced inhibition of the intestinal motility is not mediated through adrenergic, cholinergic and cAMP or through inhibition of the electrogenic pump. Compared to thiamphenicol (TAP), CAP, with a p-NO2 group in its structure, exhibited more pronounced alteration of both intestinal motility and Ca(++)-ATPase activity. We, therefore, suggest that greater inhibition of ileal motility induced by CAP is possibly a p-NO2-cGMP-Ca(++)-ATPase-mediated mechanism.

A selective NK‐2 antagonist blocks the increase of canine colonic tone and ileal contractions induced by the NK‐2 selective receptor agonist, [βAla8] neurokinin A‐(4–10)

The regulatory roles of tachykinins in intestinal motor function may be clarified by use of novel, stable and selective antagonists of neurokinin receptors. We studied the effects of the non-peptide NK-2 receptor antagonist SR48968 on canine colonic tone under resting conditions and after stimulation by the selective NK-2 receptor agonist [beta Ala8] neurokinin A-(4-10). Experiments were performed in three conscious female dogs. Proximal colonic tone was recorded by a barostat and intraluminal pressures were recorded in the terminal ileum. 10, 15 and 20 cm orad to the ileocaecal junction. In separate experiments, and in a random sequence, dogs received an i.v. injection of the NK-2 antagonist SR48968, 10, 100, 1000 micrograms/kg, followed after 30 min by 2 micrograms/kg of the agonist [beta Ala8] neurokinin A-(4-10). Experiments were replicated twice in each dog. The NK-2 agonist increased colonic tone, and SR48968 antagonized these effects in a dose-dependent fashion (Spearman's rank, r = 0.86; P < 0.01); antagonism was complete at the highest dose. SR48968 alone had no effect on colonic tone and ileal motility. When given during phase I or II of the interdigestive motor complex, [beta Ala8] neurokinin A-(4-10) increased ileal contractions: pre-treatment with SR48968 blocked this increase in ileal motility. When given during phase III, [beta Ala8] neurokinin A-(4-10) interrupted the motility front; this effect was not antagonized by SR48968. SR48968 antagonizes the increase in canine colonic tone and ileal motility induced by activation of NK-2 receptors. However, SR48968 by itself had no effect on the control of colonic tone and ileal motility under unstimulated conditions. SR48968 may be useful for investigating the physiological role of tachykinins on the gastrointestinal tract.

Ileal tone in humans: effects of locoregional distensions and eating

Using an electronic barostat in the human terminal ileum, we studied ileal tone in response to various stimuli in 10 healthy volunteers. Phasic activity was also measured by manometry. Graded orad (ileal) and caudad (cecal) balloon distensions did not produce any significant changes in ileal tone at all levels tested, even when a sensation of discomfort was felt. A linear relationship between pressure and volume was observed during in situ isobaric ileal distensions. Meal induced a biphasic tonic response with a brief (20 min) and immediate decrease in intrabag volume (64 +/- 7% of preprandial value, P < 0.05), followed by a prolonged increase in intrabag volume (158 +/- 10% of preprandial value, P < 0.05). A significant correlation was found between volume variations and phasic activities during the first phase (r = 0.88, P < 0.05), whereas no correlation was found during the second phase (r = 0.55, NS). The administration of glucagon induced a significant increase in intrabag volume from 45 +/- 5 to 70 +/- 8 ml (P < 0.05). We conclude that 1) regional distensions do not influence ileal tone and phasic motility, 2) the ileum does not show accommodation to distensions, and 3) meal produces an immediate increase in phasic and tonic activity followed by a prolonged relaxation.

Melatonin is involved in cholecystokinin‐induced changes of ileal motility in rats

The aim of this study was to determine, in the rat, the interaction between melatonin and cholecystokinin in the regulation of the ileal interdigestive motility. This was analyzed by the chronic electromyography technique. Ileal motility was defined by the presence of intermittent spike bursts corresponding to the contractile activity of the organ. In control rats, these spike bursts were organized in cyclic myoelectrical complexes. Each complex is characterized by two successive spiking activity phases: the irregular phase (ISA) followed by the regular phase (RSA). Pinealectomy suppressed the RSA phase so ileal motility was constituted only by the ISA phase. When melatonin (1 mg/kg i.v.) was injected into pinealectomized rats, RSA phases were immediately and definitively restored. RSA phases were also re-established when the "alimentary" type of cholecystokinin receptors (CCKA) were blocked by selective antagonists such as L364,718 or SR27897 (1 mg/kg i.v.). The latter had better brain accessibility than L364,718. Unlike the effects of melatonin, the effect of these antagonists was neither immediate (the latency is longer for L364,718 than for SR27897) nor definitive. In control rats, cholecystokinin (5 micrograms/kg i.v.) induced a characteristic long-lasting (29 +/- 2 min) excitomotor effect on the ileum. This effect was suppressed in pinealectomized rats and was restored after melatonin treatment. These results suggest that, via the central nervous system, melatonin is involved in the modulation of cholecystokinin action on ileal motility.