sincalide and Colonic-Diseases--Functional

Topics: Analgesics, Opioid; Colonic Diseases, Functional; Constipation; Diarrhea; Diverticulum, Colon; Electromyography; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Manometry; Parasympatholytics; Prostaglandins; Receptors, Cholecystokinin; Serotonin Antagonists; Sincalide; Somatostatin

Distal colonic motor activity was measured in 12 control subjects and seven constipation-predominant irritable bowel syndrome patients to examine the effects of intravenous administration of cholecystokinin. In the basal state, no significant motility differences were noted between these two groups. Following the intravenous administration of the hormone cholecystokinin, a statistically significant reduction in colonic motility in control subjects and a non-significant decrease in motility in irritable bowel syndrome patients was seen. Our results do not suggest an exaggeration of the colonic motor response to cholecystokinin occurs in irritable bowel syndrome.

Topics: Abdominal Pain; Adult; Cholecystokinin; Colon; Colonic Diseases, Functional; Constipation; Female; Gastrointestinal Motility; Humans; Informed Consent; Injections, Intravenous; Male; Manometry; Sincalide

Although colon dysmotility is recognized as a pathophysiological factor in irritable bowel syndrome (IBS), it has not been characterized. We have investigated motility patterns in IBS patients with abdominal pain and frequent defecation or diarrhea and in healthy volunteers.. A recording catheter that had six polyvinyl tubes with infusion ports was placed in the transverse, descending, and sigmoid colon under fluoroscopy. After 2-h basal recordings, motility responses to cholecystokinin octapeptide (CCK-8) and a meal were studied for 3 h. The motility index (MI) and number of high amplitude propagating contractions (HAPCs) in 10 IBS patients were compared with those of 10 controls. HAPCs were correlated with abdominal pain, and colon transit time using radio-opaque markers was determined. Using human colon muscle strips, the effect of CCK-8 on muscle contractions was also studied.. The MI and mean number and peak amplitude of HAPCs in IBS patients were significantly greater than in controls. These abnormalities paralleled markedly shortened colonic transit time. Abdominal pain coincided with >90% of HAPCs. Dose-dependent muscle contraction by CCK-8 was profoundly suppressed both by loxiglumide and atropine.. The dysmotility in this subset of IBS patients was characterized by significantly increased occurrences of powerful HAPCs that paralleled rapid colon transit and were accompanied by abdominal pain. Thus, it is suggested that this powerful contraction is one of the causes of abdominal pain. The action of CCK-8 seems to be mediated via the colon enteric nervous system.

Topics: Abdominal Pain; Adult; Aged; Colon; Colonic Diseases, Functional; Diarrhea; Fasting; Female; Gastrointestinal Motility; Gastrointestinal Transit; Humans; In Vitro Techniques; Male; Middle Aged; Muscle, Smooth; Postprandial Period; Reference Values; Sincalide

Topics: Colonic Diseases, Functional; Gallbladder; Humans; Sincalide

We have described previously that the gallbladder responds abnormally to infusions of cholecystokinin octapeptide (CCK-8) in patients with irritable bowel syndrome (IBS). To confirm these results and to examine the possible mechanisms, patients with IBS and predominant symptoms of diarrhea or constipation were compared with matched controls. During infusions of CCK-8 at one of three doses, the response of the gallbladder was measured ultrasonographically. The levels of CCK-8 reached in the peripheral circulation and degradation of the peptide in vitro and in vivo were used to evaluate metabolism of cholecystokinin. We confirmed that the gallbladders of patients with IBS responded abnormally to CCK-8; however, the differences were not due to any prereceptor event. Instead, this abnormality in IBS must be explained by an atypical response at the level of the target tissues.

Topics: Adult; Colonic Diseases, Functional; Female; Gallbladder; Humans; Kinetics; Male; Muscle, Smooth; Reference Values; Sincalide; Ultrasonography

Though the pathophysiology of the irritable bowel syndrome (IBS) is commonly attributed to dysfunction of the large intestine, evidence exists to incriminate the small bowel. In order to further explore the role of the small bowel in IBS several stimuli were applied, in an attempt to unmask the dysmotility of the jejunum and ileum. These included infusions of cholecystokinin-octapeptide (CCK-OP), a high fat meal, neostigmine and balloon distension of the ileum. Three groups (n = 8) each of age and sex matched healthy volunteers were studied; patients with IBS complained of predominant constipation (n = 8) or diarrhoea (n = 8). Patients with IBS responded excessively to stimulation by CCK-OP, fatty meal, and ileal distension. In general patients with diarrhoea were more sensitive to stimuli than those with constipation. The ileum responded more to stimulation than the jejunum. As in the large bowel, stimuli appear to unmask intestinal dysmotility in patients with IBS. Motor abnormalities were often accompanied by abdominal symptoms, raising the possibility that dysfunction of the small bowel contributes to the symptoms of IBS.

Topics: Adult; Colon; Colonic Diseases, Functional; Dietary Fats; Female; Gastrointestinal Motility; Humans; Ileum; Jejunum; Male; Manometry; Middle Aged; Neostigmine; Sincalide

We compared responses of the gallbladder to graded intravenous infusions of cholecystokinin octapeptide (CCK-OP) in normal controls (n = 8) and patients with irritable bowel syndrome (IBS) with predominant constipation (n = 8) or diarrhea (n = 8). The doses of CCK-OP ranged from subphysiological (negligible contraction of the gallbladder) to supraphysiological (90% contraction of gallbladder and abdominal side effects) amounts. All gallbladders contracted progressively in response to CCK-OP, and a Weibull model (power exponential function) described precisely the gallbladder's response to CCK-OP. Patients with IBS responded differently from normal patients; those with constipation contracted their gallbladders more and those with diarrhea contracted less in response to the peptide. Gallbladders were also stimulated with a high-fat, liquid meal; all patients' gallbladders contracted, but clear differences between groups could not be demonstrated postprandially. The results suggest that the smooth muscle of the gallbladder in IBS has an abnormal sensitivity to CCK-OP, and the results support the concept that IBS can be a generalized abnormality of the smooth muscle of the digestive tract.

Topics: Adult; Colonic Diseases, Functional; Constipation; Diarrhea; Dietary Fats; Female; Gallbladder; Humans; Male; Muscle Contraction; Muscle, Smooth; Sincalide; Ultrasonography

Gastrointestinal (GI) motility is centrally controlled through the sympathetic and parasympathetic nerves, sympathetic effects being partly mediated by beta adrenoceptors. Although beta adrenoceptor agonists and antagonists are widely used for different disorders, little is known about the influence of these agents on GI motility. The present study was initiated to investigate whether there is a physiological, beta adrenergic influence on human GI motility and to describe the effects of selective beta adrenoceptor stimulation on motility in the proximal and distal parts of the GI tract. Esophageal peristalsis was measured in healthy subjects using electronic catheters. Distal colonic motility was measured with an open-tipped, water-perfused catheter in the sigmoid colon and from an air-filled balloon in the rectum in healthy subjects and in patients with the irritable bowel syndrome (IBS). In one study, colonic motility was stimulated with continuous infusion of the octapeptide of cholecystokinin (CCK-OP). Esophagus: Peristaltic amplitude was increased in the distal smooth muscle part of the esophageal body after infusion of both the nonselective beta blocker propranolol and the beta-1 selective blocker metoprolol. After infusion of the beta-1 agonist prenalterol and the beta-2 selective agonist terbutaline, a profound decrease in esophageal peristaltic amplitude was seen. Pretreatment with metoprolol selectively blocked the response to a moderate dose of prenalterol but did not block the response to terbutaline. The latter response was blocked by propranolol. Peristaltic velocity in the proximal part of the esophagus was decreased by beta-1 stimulation and in the distal part by beta-2 stimulation. Distal colon: In healthy subjects the sigmoid motility index showed a dose-dependent increase after metoprolol and propranolol, respectively. The increase was more marked after propranolol infusion. Terbutaline decreased the sigmoid motility index both in healthy subjects and in patients with the IBS. Furthermore, the rectal motility index was decreased in the group of healthy subjects. The effects of prenalterol on rectal and sigmoid motility did not differ from those of placebo. The IBS patient group showed larger intraindividual variations in sigmoid motility from day to day and also lower rectal motility indices than the healthy subjects. Infusion of CCK-OP increased the sigmoid motility index compared to non-stimulated conditions. No effects on CCK-OP stim

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Adult; Colon; Colonic Diseases, Functional; Esophagus; Female; Gastrointestinal Motility; Humans; Male; Manometry; Metoprolol; Middle Aged; Parasympatholytics; Practolol; Prenalterol; Propranolol; Sincalide; Terbutaline