The role of opiate receptors and cholinergic neurons in the gastrocolonic response

The aim of this study was to characterize the mechanism of the gastrocolonic response to eating in healthy human volunteers. A bipolar clip electrode recorded spike activity from the distal colon. A rapid increase in colonic spike activity occurred after eating a 1000-cal meal (16.1 +/- 2.8 spike potentials/10 min, p less than 0.001). The intravenous infusion of atropine inhibited the increase in postprandial colonic motility. Intragastric administration of procaine, a local anesthetic also inhibited the gastrocolonic response to eating. After sham feeding a modified 1000-cal meal, there was no increase in the gastrocolonic response. Morphine stimulated colonic spike activity (55.3 +/- 15.1 spike potentials/10 min, p less than 0.001). Naloxone (40 microgram/kg . h) completely inhibited morphine stimulation of the colon. Naloxone also inhibited the postprandial gastrocolonic response, but did not inhibit neostigmine stimulation of colonic motility. These data suggest: (1) the gastrocolonic response is mediated by afferent neural receptors in the gastroduodenal mucosa, (2) there is no cephalic phase in the gastrocolonic response to eating, and (3) efferent cholinergic neurons and opiate receptors are both necessary for the gastrocolonic response.     

Identification of muscarinic receptor subtype mediating colonic response to eating

The colonic motor response to eating requires cholinergic transmission. Recent studies have identified two subclasses of muscarinic receptor, the M₁ and the M₂ subtype. The aim of this study was to evaluate the muscarinic receptor subtype responsible for mediating the gastrocolonic response. Spike potential (SP) activity and intraluminal pressure were recorded, during fasting and after eating a 1000-kcal mixed meal, from the distal colon of 10 healthy volunteers. In each subject three paired studies were carried out: either atropine (a nonselective antimuscarinic, 1 mg), pirenzepine (a selective M₁ antimuscarinic, 10 mg), or saline were infused intravenously before eating, using a double-blind crossover design. The meal significantly increased colonic spike potential activity (17.6±3.9, SP/30 min) above fasting values (2.7±0.6,P<0.01) in the control study. There was no postprandial increase in spike potential activity (3.3±0.9, SP/30 min) after atropine. The meal also significantly increased spike potential activity (15.4±3.3 SP/30 min,P<0.01) above fasting levels and equal to that of the controls, in the pirenzepine study. These data suggest that the colonic motor response to eating is mediated through the M₂ but not the M₁ subtype of muscarinic receptors.     

Comparison of intraluminal and intravenous mediators of colonic response to eating

Eating a 1000-kcal mixed meal stimulates an increase in distal colonic motility. Fat is the dietary component which is the major stimulant of colonic spike activity. In this study the colonic spike activity increased similarly after the mixed meal [19.1±2.4 spike potentials (SP)/30 min] and after the fat meal (19.4±5.4 SP/30 min). Fat stimulated a concentration-dependent increase in colonic motility only when in contact with the gastroduodenal mucosa. Intravenous administration of Liposyn (100 kcal/hr) did not stimulate an increase in colonic spike activity (3.3±1.3 SP/30 min) despite greater increase in plasma total fatty acid levels than after the oral ingestion of fat. In contrast both the oral ingestion and the intravenous administration of an amino acid mixture (Aminosyn) inhibited the gastrocolonic response after the 1000-kcal mixed meal. Thus, these studies demonstrate: (1) fat stimulates colonic motility only through direct mucosal contact, and (2) a mixture of amino acid inhibits colonic motility through either mucosal contact or by circulating in the plasma. The exact neurohumoral mechanisms involved in both of these effects is unknown at present.     

Role of hypothalamic cholecystokinin octapeptide in the colonic motor response to a meal in rats

The effects of hypothalamic microinfusions of cholecystokinin octapeptide and its antagonist L364,718 on cecocolonic myoelectrical activity were evaluated by electromyography in fasted and fed rats. The rats were chronically fitted with electrodes implanted on the cecum and proximal colon and cannulas placed bilaterally in either the ventromedial or lateral hypothalamus. In fasted rats, microinfusion of cholecystokinin octapeptide (10 ng/kg) into the ventromedial hypothalamus increased the spike-burst frequency of the cecum and the colon by 45.6% and 43.7%, respectively, during the 30-minute period after treatment. The injection of cholecystokinin octapeptide (10 ng/kg) into the lateral hypothalamus had no effect on either cecal or colonic motility. Feeding increased the frequency of cecal and colonic spike bursts by 52.1% and 50.1% for 30 minutes postprandially. When infused bilaterally into the ventromedial hypothalamus 10 minutes before feeding, L364,718 (1 or 5 micrograms/kg) abolished the increase of the frequency of cecal and colonic contractions induced by the meal. Infused into the lateral hypothalamus at similar dosages, L364,718 had no effect on the postprandial enhancement of cecocolonic motility. Increase of cecocolonic spike-burst frequency induced by feeding or by cholecystokinin octapeptide injected into the ventromedial hypothalamus was abolished by previous intracerebroventricular but not intraperitoneal administration of atropine (1 microgram) and 4-diphenylacetoxy-N-methylpiperidine (1 microgram), a selective muscarinic M2-receptor antagonist. In contrast, pirenzepine (1 microgram, intracerebroventricularly) did not significantly reduce the meal- or cholecystokin octapeptide-induced increase in cecal and colonic motility. These results suggest that, in rats, (a) cholecystokinin octapeptide is involved in the generation of the cecocolonic motor response to a meal and these effects are mediated through cholecystokinin octapeptide receptors located in the ventromedial hypothalamic nuclei, and (b) these postprandial colonic motor changes involve central cholinergic activation through muscarinic M2 receptors.     

The gastrocolic response: evidence for a neural mechanism

The aim of this study is to determine the effect of anticholinergic therapy on the gastrocolonic response to a standard meal or its major constituent fat. A rapid increase in rectosigmoidal spike activity occurs after ingesting the standard meal or the fat meal (P less than 0.01). Distal colonic motility returns to fasting levels 50 min after both meals. There is no further increase in spike activity after the 1000-calorie meal, but spike activity increases again 70 min after ingesting the fat (P less than 0.02). The anticholinergic drug, clidinium bromide, inhibits the early increase in spike activity after both meals. However, the anticholinergic has no effect on the delayed peak of activity following the ingestion of fat. This study suggests that (a) the early gastrocolic response to a standard meal and a fat meal is cholinergically mediated and (b) the late increase in rectosigmoidal motility occurs only after fat ingestion and may be controlled by other neural mediators or possibly the gastrointestinal hormones.     

Central and peripheral control of postprandial pyloric motility by endogenous opiates and cholecystokinin in dogs

The role of endogenous opiates and cholecystokinin (CCK) in the control of postprandial pyloric myoelectric activity was investigated in conscious dogs with chronically implanted intraparietal electrodes at the gastroduodenal junction. Meals consisted of either 20 g/kg of canned food (standard meal) or the same food supplemented with 0.5 mL/kg of arachis oil (fat meal). During the 6 hours after standard and fat meals, the number of pyloric spike bursts, 2-4 seconds in duration, was 61.8 +/- 15.8 and 49.9 +/- 12.7/15 minutes, respectively. Administered 15 minutes before a fat meal, naloxone (50 micrograms/kg IV) decreased the number of spike bursts by 31.4%, whereas methyl-levallorphan, a peripheral opiate antagonist, increased postprandial spike activity by 22.2% when administered IV (0.5 mg/kg) and decreased it when administered intracerobroventricularly at a dose of 10 micrograms/kg. These two antagonists administered in the same conditions before a standard meal had no effect on the postprandial spike activity. A 1-hour infusion of cholecystokinin octapeptide (CCK-8), 500 ng.kg-1.h-1 IV and 50 ng.kg-1.h-1 intracerebroventricularly, performed 1 hour after a standard meal induced a 19.6% and 15.8% decrease in the number of pyloric spike bursts, respectively. Both naloxone IV (50 micrograms/kg) and methyl-levallorphan intracerebroventricularly (10 micrograms/kg) administered before the infusion of CCK-8 reinforced this pyloric inhibition, which was antagonized by methyl-levallorphan IV (0.5 mg/kg). The CCK antagonist asperlicin, 200 micrograms/kg IV and 20 micrograms/kg intracerebroventricularly, administered before a fat meal increased pyloric spike bursts by 22.0% and 31.5%, respectively. These results indicate that after a fat meal, endogenous opiates exert a peripheral inhibitory and central stimulatory control of pyloric motility; they suggest the involvement of both peripheral and central release of CCK.     

Effect of secoverine on colonic myoelectric activity in diverticular disease of the colon

The effect of secoverine on colonic smooth muscle was measured in pationts with diverticular disease and in healthy subjects. The frequency of slow wave activity was determined using the fast Fourier transform (FFT) and peak identification analysis (SWSA). The mean slow wave frequency was similar (6 cycles/minute) in healthy subjects using both analytic methods. The slow wave frequency in patients with diverticular disease was similar to that in healthy subjects. The peak frequency measured with SWSA was uniformly higher than that measured with FFT. Secoverine, a muscarinic antagonist, did not affect the slow wave frequency. Eating a 1000-kcal meal initiates an increase in colonic spike activity (22±2 spike potential/30 min) (P<0.001) in healthy subjects during the immediate postprandial period. The gastrocolonic response in patients with diverticular disease was prolonged for 60 min. Secoverine inhibited the gastrocolonic response in patients with diverticular disease. These studies suggest (1) patients with diverticular disease have a similar slow wave frequency as healthy subjects, (2) the gastrocolonic response is prolonged in patients with diverticular disease, and (3) secoverine inhibits the colonic response.     

Inhibition of postprandial colonic motility after ingestion of an amino acid mixture

Previous studies suggested that the ingestion of a mixture of amino acids inhibited the fatstimulated increase in colonic motility. This study determined the effect of the ingestion of an amino acid mixture on the postprandial distal colonic spike potential (SP) response to a standard 1000-calorie meal in normal subjects and in patients with the irritable bowel syndrome. The distal colonic response was measured following a standard meal with and without the preadministration of a protein hydrolysate solution. After the meal, normal subjects had their maximum response within the first 30-min postprandial period (41.0±6.3 SP/30 min). Spike activity returned to fasting activity by 60 min. Most patients with irritable bowel syndrome did not have a significant early postprandial distal colonic spike response (P>0.05), but all patients had a large late increase in spike activity occurring 60–90 min postprandially (50.0±5.0 SP/30 min) (P<0.001). Ingestion of the protein hydrolysate solution prior to the meal resulted in suppression of the early colonic spike response in normal subjects (P<0.01) and the late colonic spike response in the irritable bowel patients (P<0.01). This study suggests that amino acids can modulate postprandial colonic motility and that dietary alteration may be beneficial in the irritable bowel syndrome.Presented at the National meeting of the American Gastroenterological Association, May 21, 1979, New Orleans, Louisiana.     

Influence of papaverine on bethanechol or OP-CCK stimulation of feline colonic muscle

Papaverine relaxes smooth muscle from various organ systems throughout the body. The purpose of this study was to determine the effects of papaverine on colonic smooth muscle from the transverse colon of the cat. Myoelectrical activity was recorded with monopolar glass pore electrodes. Papaverine was administered alone and simultaneously with bethanechol or the octapeptide of cholecystokinin. Higher concentrations of papaverine (10(-4) M, 10(-5) M) abolished both slow-wave activity and migrating spike bursts. Lower concentrations of papaverine (10(-6) M) had no effect on slow waves or the migrating spike burst. Bethanechol (10(-6) M) or OP-CCK (4 x 10(-9) M, 4 x 10(-10) M) stimulated spike activity (p < 0.001). Papaverine (10(-6) M had a minimal effect on the increase in spike activity that occurred after octapeptide of cholecystokinin in a concentration of 4 x 10(-10) M (p < 0.05). Papaverine had no effect on the stimulation of the colonic smooth muscle by 4 x 10(-10) M octapeptide of the colonic smooth muscle by 4 x 10(-9) M octapeptide of cholecystokinin. These studies show that (a) papaverine can inhibit smooth muscle myoelectrical activity, (b) papaverine is a potent inhibitor of cholinergic stimulation of colonic smooth muscle, but (c) papaverine has a minimal effect on octapeptide of cholecystokinin stimulation of the isolated colonic smooth muscle.     

Abnormal gastrocolonic response in patients with ulcerative colitis.

The purpose of these studies is to determine the colonic myoelectrical and contractile response after eating a 1000 calorie meal in patients with active ulcerative colitis. During fasting, slow waves are identifiable significantly more in patients with ulcerative colitis than in normal subjects (p < 0 . 01). The predominant slow wave frequency is 6 . 1 +/- 0 . 2 cycles/min, which is similar to the normal subjects. The slow waves are not altered by eating in either group. Minimal spike or contractile activity occurs during the fasting period both in patients with ulcerative colitis and in normal subjects. In patients with ulcerative colitis, spike activity increases rapidly after eating the 1000 calorie meal (P < 0 . 01), but the maximal response is decreased and shorter in duration than in normal subjects. There is no simultaneous increase in colonic contractility above fasting levels after the meal in patients with ulcerative colitis. This is strikingly different from the simultaneous increase in contractile and spike activity (P < 0 . 01) that occurs after eating in normal subjects. These studies suggest that in ulcerative colitis (1) the colonic smooth muscle slow wave activity is intact; and (2) a disturbance in the normal colonic contractile response to eating is present despite an adequate spike response. This lack of colonic contractility may contribute to the increase in diarrhoea that occurs in these patients after eating.     

Nifedipine Reduces the Colonic Motor Response to Eating in Patients with the Irritable Colon Syndrome

Patients with the irritable colon syndrome have an exaggerated and/or prolonged colonic motor response to eating. This is believed to be the cause of their postprandial complaints. Since the flux of calcium ions across cell membranes plays a major role in the contractions of the gastrointestinal smooth muscle, we investigated the effect of nifedipine, a calcium channel blocker, on the gastrocolonic response in nine patients with the irritable colon syndrome. Colonic myoelectric and contractile activity was recorded during fasting and after a 1000-cal mixed meal, either with or without nifedipine (20 mg sublingually) administration. Nifedipine reduced the postprandial increase of both spike potential activity and motility index. This effect of acute administration of the drug provides rational support to test nifedipine in clinical trials as a possible means for treating the irritable colon syndrome.     

Colonic manometry in children with chronic intestinal pseudo-obstruction.

Pressure changes were evaluated in the transverse, descending, and rectosigmoid colon of 30 children with chronic intestinal pseudo-obstruction. Twenty two had severe lifelong constipation and eight had symptoms suggesting a motility disorder exclusively of the upper gastrointestinal tract. Based on prior antroduodenal manometry, 24 children were diagnosed as having a neuropathic and six a myopathic form of intestinal pseudo-obstruction. On the day of study, endoscopy was used to place a manometry catheter into the transverse colon and intraluminal pressure was recorded for more than four hours. After a baseline recording, we gave a meal to assess the gastrocolonic response. Colonic contractions were noted in 24 children. The six children with no colonic contractions had a hollow visceral myopathy and constipation. In the children with colonic contractions, fasting motility did not differentiate children with and without constipation. After the meal, in all eight children without constipation there was (1) an increase in motility index (3.2 (SEM 0.3) mm Hg/min basal v 8.4 (SEM 1.1) mm Hg/min postprandial; p < 0.001), and (2) at least one high amplitude propagated contraction (HAPC). In the 16 constipated children with colonic contractions the motility index did not significantly increase after the meal (2.1 (SEM 0.3) mm Hg/min basal v 3.1 (SEM 0.4) mm Hg/min postprandial) and 12 of them had no HAPCs (p < 0.01 v group without constipation). In summary, in children with a clinical diagnosis of chronic intestinal pseudo-obstruction, constipation is associated with absence of HAPCs, and the gastrocolonic response or with total absence of colonic contractions. It is concluded that studies of colonic manometry are feasible in children and may document discrete abnormalities in those with intestinal pseudo-obstruction with colonic involvement.     

Cholecystokinin's role in regulation of colonic motility in health and in irritable bowel syndrome.

Colonic motor activity and plasma concentrations of cholecystokinin (CCK) both increase after oral intake of a meal. Thus, CCK had been thought to mediate the postprandial increase in colonic motor activity, which is termed gastrocolonic response. The present study used the substance loxiglumide, which acts as a specific antagonist at the CCK-A receptor, to evaluate this hypothesis. In the first set of experiments, eight healthy subjects were studied four times on separate days. A multilumen catheter was endoscopically placed with its tip lying in the descending colon. Motor activity was recorded by a low-compliance perfusion manometry system at six locations 60-45 cm from the anus. Basal activity was recorded for at least 2 hours to achieve steady-state conditions. The order of the following four experiments was randomized: (a) intravenous infusion of the CCK analogue cerulein at increasing doses (7.5, 15, 30, and 60 ng/kg.h, each given for 30 minutes); (b) intravenous cerulein plus 5 mg/kg.h loxiglumide; (c) a 1000-kcal solid/liquid meal consisting of regular German food; and (d) a meal plus 5 mg/kg.h loxiglumide. In the second set of experiments, eight patients with irritable bowel syndrome were studied twice on two separate days, and two experiments were performed n randomized order: (a) a 1000-kcal solid/liquid meal consisting of regular German food; or (b) a meal plus 5 mg/kg.h loxiglumide. The motor index was calculated as the area under contractions by a computerized system. The 1000-kcal meal markedly increased colonic motor activity. This gastrocolonic response was significantly greater in patients with irritable bowel syndrome than in healthy volunteers. Cerulein stimulated motor activity only at pharmacological doses (30-60 ng/kg.h), which resulted in plasma CCK levels markedly exceeding postprandial values. Loxiglumide abolished the effects of cerulein even at pharmacological doses. However, loxiglumide did not inhibit the gastrocolonic response to a regular meal either in healthy volunteers or in patients with irritable bowel syndrome. Loxiglumide also failed to alter the interdigestive colonic motor activity. Therefore, effects mediated by the CCK-A receptor do not play a major physiological role in the regulation of the interdigestive and postprandial motility of the left colon.     

Role of cholecystokinin and the cholinergic system in intestinal stimulation of gallbladder contraction in man

To determine the role of cholecystokinin and the cholinergic system in intestinal stimulation of gallbladder contraction, we studied the effects of atropine on plasma cholecystokinin and gallbladder contraction in six healthy volunteers (four men and two women aged 20 to 27 yr). Effects were noted after intraduodenal fat instillation and after dosage with exogenous cholecystokinin inducing plasma cholecystokinin concentrations similar to those after intraduodenal fat instillation. At regular intervals before and after administration of each stimulus, plasma cholecystokinin concentrations and gallbladder volumes were measured by radioimmunoassay and real-time ultrasonography, respectively. Intraduodenal infusion of 250 ml 20% Intralipid induced a peak plasma cholecystokinin increment of 10.2 +/- 1.6 pmol/L compared with 10.7 +/- 0.7 pmol/L during infusion of 1 Ivy dog unit per kilogram per hour of cholecystokinin. The increases in plasma cholecystokinin after fat and exogenous cholecystokinin administration were accompanied by similar decreases in gallbladder volume. Integrated gallbladder contraction after fat instillation was 3,939% +/- 288%.min compared with 3,301% +/- 359%.min during cholecystokinin infusion (NS). Atropine (0.015 mg/kg as bolus followed by 0.005 mg/kg/hr) did not change plasma cholecystokinin concentrations but induced similar inhibition of gallbladder contraction to 2,296% +/- 511%.min (p less than 0.05) after intraduodenal fat instillation and to 1,756% +/- 456%.min (p less than 0.05) during cholecystokinin infusion. We conclude that cholecystokinin is of major importance in intestinal stimulation of gallbladder contraction. Atropine inhibits the gallbladder response to intraduodenal fat. This inhibition is not due to a reduction in cholecystokinin secretion but to a diminished gallbladder response to cholecystokinin.     

Postoperative colonic motility after tropisetron and a standardized meal in patients undergoing conventional colorectal surgery

Background Early postoperative enteral nutrition is advantageous for the recovery of colonic motility but may be limited by abdominal distension, nausea, and vomiting. We aimed to investigate the tolerance of a standardized meal after pretreatment with the 5-hydroxytryptamine-3-receptor antagonist tropisetron and to study the concomitant colonic motility. Methods Colonic motility and tone were recorded on postoperative day 1 to 3 with a combined manometry/barostat recording catheter in 12 patients who underwent open colorectal surgery with an anastomosis in the distal colon or rectum. The study protocol consisted of 30 min of baseline recordings followed by 5 mg of tropisetron intravenously. Then, motility was recorded for another 30 min before patients ingested a standardized meal to trigger the gastrocolonic response. Postprandial motility was recorded for the subsequent 60 min. Results The colonic motility index increased after administration of tropisetron on all three postoperative days (day 1: 34±11 vs 122±48, day 2: 55±19 vs 101±25, and day 3: 42±16 vs 93±33 mmHg/min; p<0.05). No further increase of the motility index was observed postprandially. Frequency and amplitude of contractions were virtually unaffected by tropisetron and the meal. Barostat bag volume decreased postprandially in the proximal bag on the third, and in the distal bag on the first and second postoperative day (p<0.05). Patients’ condition was unaffected by the standardized meal after tropisetron administration. Conclusions Tropisetron may enhance colonic motility in the early postoperative period; however, the gastrocolonic response was impaired thereafter. High caloric food intake is well tolerated early after surgery after tropisetron pretreatment. This work was presented as an oral presentation at the Ross Residence Conference during the annual meeting of the Society for Surgery of the Alimentary Tract in 2001 and is published in abstract form (Gastroenterology 2001; 120(Suppl 1):A473).     

Colonic motility and gastric emptying in patients with irritable bowel syndrome effect of pretreatment with octylonium bromide

This study was undertaken to evaluate (1) the colonic response to eating for a prolonged time in healthy subjects and patients with the irritable bowel syndrome (IBS); (2) the effect of octylonium bromide, a new smooth muscle relaxant acting by interfering with calcium ion mobilization, on the postprandial colonic motility; and (3) whether chronic gastric stasis could be responsible for both the dyspeptic symptoms often complained of by IBS patients and the faulty colonic response to eating. The colonic response to a 1000-kcal mixed meal in ten healthy subjects was characterized by two transient (from 0 to 60 and from 120 to 150 min postprandially, respectively) increases in colonic motor activity; ten IBS patients showed a continuous postprandial increase in colonic motor activity that was not terminated 180 min after eating. Treatment of IBS patients with octylonium bromide (80 mg, qid,per os) for 5–7 days reduced their colonic response to eating to a very short increase in colonic motor activity limited to the first 30 min. Finally, gastric emptying was not different in the two groups.     

Cephalic stimulation of gallbladder contraction in humans: role of cholecystokinin and the cholinergic system

To determine the role of cholecystokinin and the cholinergic system in cephalic stimulation of gallbladder contraction and to compare the degree of gallbladder contraction by cephalic stimulation with postprandial gallbladder contraction, 8 healthy volunteers (4 males, 4 females, 20-65 years) underwent the following studies: sham feeding of an appetizing meal, sham feeding with intravenous atropine, and ingestion of the same meal. Gallbladder volume was measured by real-time ultrasonography and plasma cholecystokinin by a sensitive and specific radioimmunoassay using antibody T204. Gallbladder contraction in response to sham feeding, 30 +/- 4% (p = 0.0001 vs. basal), amounted to half of that seen after real feeding, 69 +/- 5% (p less than 0.0001 vs. basal). Significant dissociation between gallbladder response to sham feeding and real feeding was seen from 40 min (p less than 0.005-p = 0.0001). Atropine did not affect basal gallbladder volume but completely abolished gallbladder contraction in response to sham feeding. Neither sham feeding without nor sham feeding with atropine significantly affected plasma cholecystokinin levels. On the other hand, real feeding induced significant increases in plasma cholecystokinin from a basal level of 2.3 +/- 0.1 pM to a peak value of 5.9 +/- 0.4 pM at 40 min. It is concluded that an important cephalic phase of postprandial gallbladder contraction exists which is cholecystokinin-independent but dependent on a cholinergic mechanism.     

Influence of naloxone, atropine, and metoclopramide on ethanol augmentation of insulin secretion after intravenous glucose stimulation

The effect of naloxone (opiate antagonist), atropine (muscarinic antagonist), and metoclopramide (dopamine antagonist) upon ethanol augmentation of insulin secretion after intravenous glucose stimulation was studied in 19 young healthy subjects. Intravenous glucose tolerance tests were performed with and without pretreatment with oral ethanol. The effect of naloxone, atropine, and metoclopramide on insulin secretion was investigated in six, six, and seven subjects, respectively. Ethanol pretreatment was followed by increased insulin (p less than 0.001) and C-peptide areas (p less than 0.01) after intravenous glucose (0-10 min), indicating that ethanol augments insulin secretion. Neither antagonism with naloxone nor with atropine or metoclopramide was able to suppress the ethanol augmentation of insulin secretion. The decline in glucagon concentration normally seen after intravenous glucose administration was partially prevented by ethanol pretreatment.     

Motility disorders in the irritable bowel syndrome

Specific abnormalities of colonic and small bowel motility are identifiable and associated with symptoms in IBS. Characteristic abnormalities in colonic motility include a prolonged increase in 3-cycles/min colonic motor activity after a meal, an exaggerated increase in 3-cycles/min motor activity in response to stressors and CCK, and increased visceral sensitivity and motor activity in response to balloon distention. Symptoms in patients with IBS correlate in some cases with the abnormal gastrocolonic response and with pain induced by distention at various sites in the colon. Small bowel motility abnormalities identified reproducibly in IBS include an increase in daytime jejunal DCCs, an increase in daytime ileal PPCs, and more frequent cycling of daytime MMCs (in diarrhea-predominant IBS only). DCCs and PPCs are strongly associated with symptoms in IBS, and PPCs associated with altered ileocecal transit may be an important mechanism of symptoms in some patients with IBS. Esophageal and gastroduodenal motility abnormalities are inconsistently identified in IBS, and most symptoms in IBS appear to be secondary to small bowel or colonic dysfunction. Because of the paroxysmal nature of these motor abnormalities in IBS, prolonged motility recordings are required to better understand the pathophysiology of this syndrome. Patients with IBS may have altered visceral sensation and changes in afferent reflex mechanisms that modulate GI motility. These patients do not have a generalized increase in pain perception, but may have a distinct sensitivity to visceral afferent stimulation in both gastrointestinal and other viscera. Whether the altered "setpoint" to visceral afferent stimulation in IBS is intrinsic to the smooth muscle of viscera or secondary to CNS and ANS modulation is not known. Many of the symptoms and abnormalities of small bowel and colonic motility in IBS probably result from these changes in afferent sensation and reflex mechanisms. These findings support the concept that IBS is an abnormality of intestinal motility in conjunction with a "sensitive" gut.     

Plasma cholecystokinin, plasma peptide YY and gallbladder motility in patients with slow transit constipation: effect of intestinal stimulation

BACKGROUND/AIM: Because cholecystokinin and peptide YY are gut hormones with potent effects on gastrointestinal motility, we determined whether abnormalities of cholecystokinin and peptide YY exist in slow transit constipation. METHODS: Plasma concentrations of these hormones before, during and after intraduodenal infusion of a liquid meal in 21 patients with slow transit constipation were compared with the results in 8 healthy controls. RESULTS: Fasting levels of plasma cholecystokinin (3.1+/-0.2 vs. 2.4+/-0.2 pM; p = 0.02) were higher in patients. Basal plasma peptide YY (11.4+/-1.4 vs. 8.9+/-0.7 pM; p = 0.1) tended to be higher in patients. After the meal (60-90 min), incremental cholecystokinin (p<0.05), but not peptide YY, was significantly higher in patients. During intraduodenal infusion of the meal (0-60 min), incremental plasma cholecystokinin (251+/-20 pM.min) and peptide YY (1,146+/-186 pM. min) in patients were almost similar to control values (262+/-22 and 901+/-166 pM. min). Gallbladder volumes before, during and after the meal were not different between the 2 groups. Gastric emptying of a solid meal was delayed in the majority of patients (12 of 18). Abnormalities of plasma cholecystokinin were observed only in patients with delayed gastric emptying. CONCLUSION: Plasma levels of cholecystokinin are elevated in the fasting state and decrease more slowly after stimulation, but maximum release in response to intestinal nutrients is not altered in patients with slow transit constipation. The abnormality seems to be confined to a subgroup of patients with delayed gastric emptying.