sincalide and Dyspepsia

Topics: Adult; Analysis of Variance; Double-Blind Method; Dyspepsia; Female; Gastric Emptying; Humans; Male; Middle Aged; Proglumide; Receptors, Cholecystokinin; Sincalide; Time Factors

The actions of cholecystokinin (CCK) on gastrointestinal functions occur mainly via paracrine effects on peripheral sensory vagal fibers, which engage vago-vagal brain stem circuits to convey effector responses back to the gastrointestinal tract. Recent evidence suggests, however, that CCK also affects brain stem structures directly. Many electrophysiological studies, including our own, have shown that brain stem vagal circuits are excited by sulfated CCK (CCK-8s) directly, and we have further demonstrated that CCK-8s induces a remarkable degree of plasticity in GABAergic brain stem synapses. In the present study, we used fasted, anesthetized Sprague-Dawley rats to investigate the effects of brain stem administration of CCK-8s on gastric tone before and after activation of the esophageal-gastric reflex. CCK-8s microinjected in the dorsal vagal complex (DVC) or applied on the floor of the fourth ventricle induced an immediate and transient decrease in gastric tone. Upon recovery of gastric tone to baseline values, the gastric relaxation induced by esophageal distension was attenuated or even reversed. The effects of CCK-8s were antagonized by vagotomy or fourth ventricular, but not intravenous, administration of the CCK-A antagonist lorglumide, suggesting a central, not peripheral, site of action. The gastric relaxation induced by DVC microinjection of CCK-8s was unaffected by pretreatment with systemic bethanecol but was completely blocked by NG-nitro-L-arginine methyl ester, suggesting a nitrergic mechanism of action. These data suggest that 1) brain stem application of CCK-8s induces a vagally mediated gastric relaxation; 2) the CCK-8s-induced gastric relaxation is mediated via activation of nonadrenergic, noncholinergic pathways; and 3) CCK-8s reverses the esophageal-gastric reflex transiently.

Topics: Animals; Brain Stem; Cholecystokinin; Dose-Response Relationship, Drug; Dyspepsia; Esophagus; Fasting; Male; Microinjections; Neural Inhibition; Peptide Fragments; Rats; Rats, Sprague-Dawley; Reflex; Stomach; Vagus Nerve

Cholecystokinin regulates gut motility and visceral sensation. The aim of the study was to determine the diagnostic value of plasma cholecystokinin octapeptide (CCK-8) concentration in children with functional abdominal pain (FAP).. Fifty-two children (33 girls and 19 boys) aged 6-17 years with chronic abdominal pain were included in this study. On the basis of clinical data, results of endoscopy and Criteria for Functional Disorders the patients were divided into three groups: group 1--functional dyspepsia (FD), group 2--irritable bowel syndrome (IBS), group 3--non-specific FAP. The control group consisted of children without abdominal pain in anamnesis. CCK-8 concentrations in plasma were measured with radio immunoassay technique, after plasma extraction. In study protocol we analysed CCK-8 levels in fasting state and 15, 30, 60 minutes after a standard test meal.. In the fasting state plasma levels of CCK-8 were similar in each group and in controls. In the IBS patients CCK-8 levels were not increased after meal. In groups 1, 3 and controls postprandial levels were higher when compared to fasting state (p<0.05). Area under curve of CCK-8 plasma concentration was the lowest in group 2, but not significant compared to controls and other groups. No correlation was found between main symptoms of FD and IBS and CCK-8 concentration in plasma.. We conclude that gut dysmotility and symptoms of functional abdominal pain in children are not concerned with alteration of plasma CCK-8 levels before and after meal.

Topics: Abdominal Pain; Adolescent; Area Under Curve; Child; Dyspepsia; Endoscopy; Fasting; Female; Humans; Irritable Bowel Syndrome; Male; Radioimmunoassay; Sincalide

Early satiety and postprandial epigastric fullness are common symptoms in functional dyspepsia. Cholecystokinin (CCK), a mediator of satiety in humans, may be responsible for these symptoms through an increased effect on delaying gastric emptying.. In five normal subjects and in five patients, gastric emptying of inert liquid mixed with technetium (Tc99m) was studied during i.v. perfusion of normal saline and of physiological concentrations of CCK octapeptide.. Administration of CCK significantly delayed emptying of inert liquid in patients and in normal subjects, and the effect was of similar magnitude in the two groups: residual gastric volumes at 90 min increased from 9.9 +/- 6.1 to 32.1 +/- 6.2% (p < 0.025) in controls and from 9.8 +/- 4.4 to 32.2 +/- 4.7% (p < 0.005) in patients during saline infusion in comparison with CCK infusion; also, prolongation of half emptying time was not different between the two groups (19.4 +/- 1.9 min to 39.4 +/- 15.2 min in controls and 19.5 +/- 3.0 min to 31.4 +/- 7.9 min in patients).. We conclude that CCK at physiological concentrations acts similarly in normal subjects and in patients with functional dyspepsia; this suggests that, if this hormone is normally released after a meal, a peripheral action of CCK through delayed gastric emptying is not responsible for increased postprandial satiety in functional dyspepsia.

Topics: Adult; Case-Control Studies; Cholecystokinin; Dyspepsia; Female; Gastric Emptying; Humans; Sincalide; Sodium Chloride; Technetium Tc 99m Sulfur Colloid; Time Factors; Water

Topics: Adolescent; Adult; Double-Blind Method; Duodenal Ulcer; Dyspepsia; Female; Gastric Emptying; Humans; Infusions, Intravenous; Male; Middle Aged; Reference Values; Sincalide