cholecystokinin and Gastroesophageal-Reflux

Although proton pump inhibitors have become the mainstay of treatment in gastro-oesophageal reflux disease (GORD), there are still unmet needs in the management of this very common disorder. For example, all current proton pump inhibitors have a relatively slow onset of action and their activity is limited mainly to the post-prandial period with far less effective inhibition of nocturnal acid secretion. In order to achieve more potent, rapid and sustained acid inhibition several compounds are currently under development, such as new proton pump inhibitors with a prolonged plasma half-life, potassium competitive ATPase blockers (PCABs), histamine H3 agonists, and gastrin antagonists. Acid suppression does not, however, cure the disease and relapses are frequently observed after discontinuation of proton pump inhibitor therapy. Among the different abnormalities involved in the pathophysiology of this multifactorial disease, transient lower oesophageal sphincter relaxations represent the major mechanism responsible for episodes of reflux. Baclofen, the prototype GABA(B) receptor agonist, is one of the most potent inhibitors of transient lower oesophageal sphincter relaxations identified. To date the transfer of these relaxation-controlling pharmacological agents into clinical practice has however been hampered by the occurrence of unacceptable side effects. Beside "anti-relaxation therapy", the potential of novel prokinetics such as motilin agonists has been explored, especially since the motilin receptor has been cloned. Thus far the broad therapeutic value of prokinetics in GORD does, however, seem very limited in terms of efficacy with respect to oesophageal motility and acid exposure. Lastly, further research is necessary to better understand the complex mechanisms involved in oesophageal sensitivity and mucosal defence.

Topics: Animals; Cholecystokinin; Cholinergic Antagonists; Esophageal Sphincter, Lower; GABA Agonists; Gastric Acid; Gastroesophageal Reflux; Gastrointestinal Agents; Gastrointestinal Motility; Histamine Agonists; Humans; Morphine; Muscle Relaxation; Nitric Oxide Synthase; Proton Pump Inhibitors; Receptor, Cholecystokinin B

Transient lower esophageal sphincter relaxations (TLESRs) are the major mechanism of reflux in patients with gastroesophageal reflux disease. They are therefore attractive targets for pharmacotherapy. During the past 5 years, there has been a burgeoning interest in the neural pathways that control these events and in the pharmacologic receptors involved in these pathways. Several agents have been shown to reduce the rate of TLESRs, including cholecystokinin-A antagonists, anticholinergic agents, nitric oxide synthase inhibitors, morphine, somatostatin, serotonin type 3-receptor antagonists, and gamma-aminobutyric acid-B (GABA(B)) agonists. Their predominant site of action appears to be on either the afferent pathways and/or the central integrative mechanisms within the dorsal vagal complex in the brainstem. Most of the agents tested are unsuitable for clinical use either because of side effects or because of the lack of an orally effective formulation. The most promising agents identified to date are the GABA(B) agonists. Baclofen, the prototype GABA(B) agonist, inhibits the rate of TLESRs by more than 50%. Control of TLESRs is a major new approach to the treatment of reflux disease. It is likely to be applicable to the majority of patients, particularly those without macroscopic mucosal lesions or only mild erosive disease. Further development of more effective agents will depend both on a better understanding of the neural pathways and receptors involved in the control of TLESRs, as well as on investigation of other novel agents. At present, inhibition of TLESRs is at the threshold of transition from concept to practical use. Whether it makes the final leap into the mainstream of therapy will depend on the development of new, novel, and well-targeted pharmacologic agents.

Topics: Cholecystokinin; Cholinergic Antagonists; Clinical Trials as Topic; Esophagogastric Junction; GABA Antagonists; Gastroesophageal Reflux; Humans; Morphine; Muscle Relaxation; Nitric Oxide; Parasympatholytics; Sensitivity and Specificity; Treatment Outcome

Gastro-oesophageal reflux (GOR) is common. Nearly all healthy individuals experience occasional or frequent reflux episodes, with or without symptoms, which occur during spontaneous relaxations of the lower oesophageal sphincter, predominantly after meals. It is not known how neural, hormonal and muscular factors contribute to this. A proportion of the patients with reflux disease have normal lower oesophageal sphincter pressures, and their reflux episodes occur during spontaneous sphincter relaxations following the pattern of normals. Nevertheless, most patients with reflux disease have decreased lower oesophageal sphincter pressure, and manoeuvres which increase the intraabdominal pressure provoke "stress" reflux. If the sphincter pressure is very low, "free" reflux occurs; the cause of decreased sphincter pressure is not known. Pharmacological and gastric factors also facilitate GOR. The noxious potency of reflux material on the oesophageal epithelium depends on its components [( H+], pepsin, bile salts, trypsin) and the contact time, which is prolonged during supine and nocturnal reflux episodes, i.e. when clearance function is impaired. In complicated reflux disease it is necessary to consider this multifactorial model of the pathogenesis of reflux disease, and to go on to more sophisticated diagnostic procedures (manometry, scintiscanning, prolonged pH-monitoring) in order to identify an individual patients' predominant pathogenetic factor.

Topics: Cholecystokinin; Esophagitis, Peptic; Esophagogastric Junction; Esophagus; Gastric Emptying; Gastrins; Gastroesophageal Reflux; Hernia, Hiatal; Histamine H2 Antagonists; Humans; Manometry; Middle Aged; Peristalsis; Pressure

The patient with gastric ulcer (GU) has abnormal reflux of bile-containing duodenal contents into the stomach. Antral gastritis is prominently associated with GU and is more extensive with severe reflux and with ulcer chronicity and probably when bile salts are accompanied by other constituents of duodenal fluids. Smoking is significantly associated with GU, and it produces reflux in normal subjects and in patients with duodenal ulcer, which in turn is commonly associated with GU. Reflux has not been shown to precede either the gastritis or the gastric ulcer and probably persists despite ulcer healing. The pyloric spincter in the patient with GU probably contracts subnormally to endogenous or exogenous secretin or CCK. This can be explained by associated hypergastrinemia since antral acidification improves the response. Because the pylorus may be usually open, abnormal reflux may be related as much or more to disturbances of other gastroduodenal functions known to control the movement of chyme through what may be a relatively passive pyloric zone. Speculation from animal models implicates bile reflux in aspirin-induced and shock-related gastric ulceration and assigns to bile a possible explanation, in part at least, for the apparent therapeutic efficacy of a carbenoxalone derivative and an antipepsin agent. Similar speculation warrants a search in the patient with GU for abnormalities of gastroduodenal peristalsis-related electric activity and for impaired release of secretin, possibly from antral cells of production. Possible abnormal purinergic inhibition of the gastric fundus and pylorus also warrants further study.

Topics: Animals; Bile; Cholecystokinin; Disease Models, Animal; Duodenum; Gastric Mucosa; Gastrins; Gastritis; Gastroesophageal Reflux; Humans; Pyloric Antrum; Pylorus; Secretin; Stomach Ulcer

Topics: Animals; Cholecystokinin; Esophageal Achalasia; Esophagogastric Junction; Gastrins; Gastroesophageal Reflux; Gastrointestinal Motility; Hernia, Diaphragmatic; Humans; Pentagastrin; Pressure; Secretin

Fats cause reflux symptoms in many patients and cholecystokinin (CCK) may play a role. This study was designed to evaluate the effects of intraduodenal nutrient infusion on serum CCK levels, lower esophageal sphincter (LES) pressure, and gastroesophageal reflux (GER).. Twenty-four asymptomatic volunteers were studied. A Dent sleeve catheter assessed LES function while an impedance-pH catheter measured reflux events. Participants were randomized to fat (F), carbohydrate (C) or protein (P) infusion. Serum CCK and LES pressures were measured at baseline and after nutrient infusion.. Baseline LES pressures and CCK levels were similar in all three groups. A significant linear decrease was found in LES pressure during F, but not C or P, infusion (P=0.004). A significant interaction effect was noted between the infusion groups and CCK levels (P=0.002). A significant linear increase was noted in CCK levels during F but not during C or P infusion (P=0.02). A significant inverse correlation was found between CCK levels and LES pressure (ρ=-0.43; P=0.04). Esophageal acid exposure was significantly increased in the F infusion group (median; interquartile range: 1.10%; 0.25-4.7%) compared to both the C (0.03%; 0.00-0.39%) and P infusion (0.03%; 0.00-0.39%) groups (P=0.04).. Intraduodenal F infusion was associated with an increase in CCK levels, while P and C were not. LES pressure decreased significantly after fat infusion and reflux events were more frequent. Fat-induced CCK release is another mechanism that contributes to GER.

Topics: Adult; Catheters; Cholecystokinin; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Esophageal Sphincter, Lower; Female; Food; Gastroesophageal Reflux; Humans; Incidence; Male; Pressure

Colonic fermentation of carbohydrates is known to influence gastric and esophageal motility in healthy subjects. This study investigated the effects of colonic fermentation induced by oral administration of fructooligosaccharides (FOS) in patients with gastroesophageal reflux disease (GERD).. In the cross-over design used in the study, 9 patients with symptomatic GERD were administered a low-residue diet (i.e., 10 g fiber/day) during 2, 7-day periods, receiving either 6.6 g of FOS or placebo 3 times daily after meals. Each period was separated by a wash out of at least 3 weeks. On day 7, esophageal motility and pH were recorded in fasting conditions and after a test meal containing 6.6 g of FOS or placebo. Breath hydrogen concentrations (reflecting colonic fermentation) and plasma concentrations of glucagon-like peptide 1 (GLP-1), peptide YY, and cholecystokinin were monitored.. Compared with placebo, FOS led to a significant increase in the number of transient lower esophageal sphincter relaxations (TLESRs) and reflux episodes, esophageal acid exposure, and the symptom score for GERD. The integrated plasma response of GLP-1 was significantly higher after FOS than placebo.. Colonic fermentation of indigestible carbohydrates increases the rate of TLESRs, the number of acid reflux episodes, and the symptoms of GERD. Although different mechanisms are likely to be involved, excess release of GLP-1 may account, at least in part, for these effects.

Topics: Administration, Oral; Adult; Breath Tests; Cholecystokinin; Colon; Cross-Over Studies; Diet; Esophagogastric Junction; Female; Fermentation; Gastroesophageal Reflux; Glucagon; Glucagon-Like Peptide 1; Humans; Hydrogen; Male; Middle Aged; Oligosaccharides; Patient Compliance; Peptide Fragments; Peptide YY; Postprandial Period; Protein Precursors

Gallbladder removal is associated with an increased incidence of gastroesophageal reflux, but the mechanism is unclear. Cholecystokinin (CCK) release, which causes gallbladder contraction, is inhibited by bile in the duodenum. This study investigates the effect of cholecystectomy on meal-stimulated CCK secretion.. Three groups of patients were studied. Group 1 (n = 15) were normal controls. Group 2 (n = 27) were patients with symptomatic gallstones. Group 3 (n = 25) were patients who had undergone cholecystectomy. Meal-stimulated CCK levels were measured by radioimmunoassay at defined time points for 60 min after a standard corn oil-based meal.. Fasting CCK levels were similar in all three groups. In postcholecystectomy patients, meal-stimulated plasma CCK levels were significantly elevated compared with controls: median (range) integrated CCK values for 60 min were 116 (28-209) in controls, 123 (20-501) in gallstone patients, and 176 (63-502) after cholecystectomy.. This study suggests that cholecystectomy causes an exaggerated meal-stimulated CCK response. Because CCK is known to relax the lower esophageal sphincter. these findings may help explain the increased incidence of gastroesophageal reflux seen after cholecystectomy.

Topics: Adult; Aged; Cholecystectomy; Cholecystokinin; Cholelithiasis; Eating; Female; Gallbladder; Gastroesophageal Reflux; Humans; Male; Middle Aged; Postprandial Period; Radioimmunoassay; Time Factors

Postprandial acid reflux is thought to be mediated by the increase in transient lower oesophageal sphincter relaxations (TLOSR) frequency and fall in lower oesophageal sphincter (LOS) pressure seen after ingestion of a meal. Studies in animals and healthy volunteers suggest that cholecystokinin (CCK) may play a role.. To study the role of CCK in postprandial LOS function using the CCK antagonist loxiglumide.. 10 asymptomatic volunteers (7 male, 20-29 years) and 9 patients with symptomatic gastro-oesophageal reflux (4 male, 33-66 years).. Oesophageal, LOS and gastric pressure and oesophageal pH readings were recorded for 1 h before and 2 h after intragastric infusion of a 200 kCal, 300 mL long chain triglyceride meal. Each subject underwent two studies and received intravenous loxiglumide or placebo infusion in randomized order.. During placebo infusion, postprandial LOS pressure fell [volunteers: 17 (9-31) to 7 (1-19) mmHg (P < 0.01), patients: 15 (6-26) to 9 (2-21) mmHg (P=0.02)] and TLOSR frequency increased [volunteers: 0 (0-1) to 2 (0-7) per hour (P=0.01), patients: 0 (0-3) to 2 (0-10) per hour (P=0.03)]. Loxiglumide infusion attenuated the postprandial fall in LOS pressure and the postprandial increase in TLOSR frequency [volunteers: 0 (0-3) per hour (P=0.04 vs. placebo), patients: 0 (0-2) per hour (P=0.03 vs. placebo)], but it had only modest effects on postprandial acid exposure [volunteers: placebo 45 (0-1725) vs. loxiglumide 0 (0-443) seconds (N.S.), patients: placebo 60 (0-3442) seconds vs. loxiglumide 31 (0-1472) seconds (N.S.)].. Loxiglumide inhibits TLOSR and attenuates the fall in LOS pressure following a meal, but has only modest effects on postprandial gastro-oesophageal acid reflux.

Topics: Adult; Aged; Cholecystokinin; Cross-Over Studies; Double-Blind Method; Esophagogastric Junction; Female; Gastroesophageal Reflux; Hormone Antagonists; Humans; Male; Middle Aged; Postprandial Period; Proglumide

Transient lower oesophageal sphincter relaxations (TLOSRs) has been found to be the main mechanism of gastro-oesophageal reflux. In dogs, cholecystokinin (CCK) is involved in their occurrence. The aim was to evaluate the role of endogenous and exogenous CCK in the occurrence of TLOSRs induced by gastric distension at constant pressure in humans.. Ten healthy volunteers were studied. Lower oesophageal sphincter pressure was monitored with a sleeve device and gastric distension was performed via an intragastric bag monitored by a barostat. During distensions, saline, CCK (30 ng/kg/h) or the CCK-A receptor antagonist loxiglumide (10 mg/kg/h) was perfused in a random double blind order.. There was no significant difference between the number of TLOSRs during the different distensions with saline; CCK increased the number of TLOSRs at a mean rate of 13.1 compared with 9.1 with saline (p < 0.001). Loxiglumide significantly decreased the number of relaxations to 5.3 versus 8.3 under paired saline infusion (p < 0.001).. In humans, CCK-A receptor subtype is involved in the occurrence of transient lower oesophageal sphincter relaxations induced by gastric distension.

Topics: Adult; Cholecystokinin; Double-Blind Method; Esophagogastric Junction; Female; Gastroesophageal Reflux; Hormone Antagonists; Humans; Male; Manometry; Pressure; Proglumide; Receptors, Cholecystokinin; Stomach Diseases

Fourteen patients with clinically obvious gastro-oesophageal reflux were examined by conventional barium meal radiology. Neither exogenous penta-gastrin nor cholecystokinin appeared to influence the radiological competence of the gastro-oesophageal junction in ten of thos patients. The remaining four patients were used as controls and normal saline was injected instead of the active preparation. Radiological competence was unaffected. The significance of these findings is discussed.

Topics: Cholecystokinin; Esophagogastric Junction; Gastroesophageal Reflux; Humans; Pentagastrin; Radiography

Of particular interest is the study of the peculiarities of clinical findings and diagnostics of gastroesophageal reflux disease (GERD) in patients with diabetes mellitus (DM). The aim of the research - to study the dynamics of cholecystokinin (CCK) level on the background of complex therapy using the ursodeoxycholic acid (UDCA) drug in patients with GERD with type 2 DM. 68 patients with combination of type 2 DM and GERD were examined. The levels of CCK were studied in these patients, depending on the clinical forms of GERD, as well as their dynamics on the background of UDCA therapy. More pronounced increase in the serum level of CCK in patients with combination of type 2 DM and extra-esophageal manifestations of GERD was observed. Decrease in the CCK level in 2,4 - 2,7 times was reached on the background of complex therapy with UDCA in patients with combination of type 2 DM and GERD (p<0,01). In patients with type 2 DM and GERD, an increase in blood serum CCK level is observed, especially in case of extra-esophageal form of reflux disease. The maximum concentration of CCK in blood serum was revealed in overweight patients with type 2 DM in case of an extra-esophageal form of GERD. The use of UDC medication in the complex treatment of patients with type 2 DM and GERD leads to a normalization tendency of blood serum CCK levels, as well as to a decrease in body mass in these patients.

Topics: Cholecystokinin; Diabetes Mellitus, Type 2; Gastroesophageal Reflux; Humans; Ursodeoxycholic Acid

  Duodenal lipid intensifies the perception of esophageal acid perfusion. Recently, we showed that genes implicated in lipid absorption were upregulated in the duodenum of fasting gastro-esophageal reflux disease (GERD) patients. This suggests that chylomicron production and secretion may be enhanced and, consequently, the release of apolipoprotein A-IV (apoA-IV), a chylomicron-derived signaling protein. ApoA-IV may stimulate release of cholecystokinin (CCK), an activator of vagal afferents. This study evaluated putative involvement of abnormal apoA-IV and CCK responses to lipid in GERD..   Ten GERD patients and 10 healthy volunteers (HV) underwent duodenal perfusion with Intralipid 20%, 2 kcal min(-1) , for 60 min. Symptoms were scored, blood samples collected every 15 min during lipid perfusion and 15 min after discontinuation when duodenal biopsies were taken. Plasma and mucosal concentrations of apoA-IV and CCK and transcript levels of 21 genes implicated in lipid absorption, differentially expressed under fasting conditions, were quantified..   Heartburn (P = 0.003), abdominal discomfort (P = 0.037) and nausea (P = 0.008) only increased significantly during lipid infusion in GERD patients. Following lipid infusion mean mucosal apoA-IV concentration was lower in GERD patients compared with HV (P = 0.023), whereas plasma concentration tended to be elevated (P = 0.068). Mean mucosal CCK concentration was also lower in GERD patients (P = 0.009). Two genes, HIBADH and JTB, were upregulated in GERD patients (P = 0.008 and P = 0.038, respectively)..   Our results suggest excessive duodenal lipid-induced release of apoA-IV and CCK in GERD. We postulate that the resulting heightened activation of duodenal vagal afferents may underlie central sensitization, thereby increasing the perception of reflux events.

Topics: Adult; Aged; Apolipoproteins A; Central Nervous System Sensitization; Cholecystokinin; Duodenum; Emulsions; Female; Gastroesophageal Reflux; Gene Expression Profiling; Humans; Lipid Metabolism; Male; Middle Aged; Phospholipids; Polymerase Chain Reaction; Soybean Oil

The effects of postprandial water intake on the gastrointestinal tract have not been systematically investigated in humans.. In 8 healthy volunteers, the gastric antral pressure was measured with a strain gauge transducer, while the esophageal and lower esophageal sphincter pressures were measured with an infused catheter with a Dent sleeve. The esophageal pH at 5 cm above the lower sphincter was measured with a microglass electrode. A standard test meal (560 kcal) was eaten and 500 ml water was ingested 1 h later. The plasma cholecystokinin level was assessed at 4-min intervals. As a control, the same study was done on another day with sham water intake.. At 4 min after water intake, there was a significant decrease in gastric antral motility and a significant increase in the plasma cholecystokinin level. Water intake also significantly increased the occurrence of gastroesophageal reflux.. The rapid increase in cholecystokinin after water intake may be initiated by a feedback mechanism related to inflow of fatty chyme into the duodenum that inhibits gastric antral activity.

Topics: Adult; Biomarkers; Cholecystokinin; Drinking; Esophageal Sphincter, Lower; Fasting; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Male; Manometry; Middle Aged; Postprandial Period; Pyloric Antrum; Radioimmunoassay; Reference Values

Topics: Aged; Cholecystokinin; Enteral Nutrition; Food, Formulated; Gastroesophageal Reflux; Gastroscopy; Gastrostomy; Humans; Jejunostomy; Male

After Nissen fundoplication, dyspeptic symptoms such as fullness and early satiety develop in >30% of patients. These symptoms may result from alterations in proximal gastric motor and sensory function.. We have evaluated proximal gastric motor and sensory function using an electronic barostat in 12 patients after successful laparoscopic Nissen fundoplications (median follow-up; 12 months). Twelve age- and gender-matched patients with severe gastroesophageal reflux disease (GERD) and 12 healthy volunteers served as controls. Studies were performed in the fasting state and after meal ingestion. Gastric emptying tests were performed in all patients. Vagus nerve integrity was measured by the response of pancreatic polypeptide (PP) to insulin hypoglycemia.. Minimal distending pressure and proximal gastric compliance were not significantly different between post-Nissen patients, GERD patients, and healthy controls. Postprandial relaxation of the stomach, however, was significantly (p < 0.05) reduced post-Nissen (267 +/- 34 ml), compared with controls (400 +/- 30 ml) and GERD (448 +/- 30 ml). Postprandial relaxation was significantly (p < 0.01) prolonged in GERD patients. Postprandial relaxation of the stomach correlated with gastric emptying of solids (r = 0.62; p = 0.01). Gastric emptying of solids became significantly (p < 0.05) faster after fundoplication. Postprandial fullness was significantly (p < 0.05) increased in the operated patients.. Post-Nissen patients have a significantly reduced postprandial gastric relaxation and significantly accelerated gastric emptying, which may explain postoperative dyspeptic symptoms. The abnormalities result from fundoplication and not from vagus nerve injury or reflux per se, because in reflux patients gastric relaxation and gastric emptying are prolonged.

Topics: Adult; Cholecystokinin; Eating; Fasting; Female; Fundoplication; Gastric Emptying; Gastrins; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Laparoscopy; Male; Middle Aged; Postoperative Period; Pressure; Sensation; Stomach; Vagus Nerve

Exogenous cholecystokinin (CCK) decreases lower esophageal sphincter (LES) pressure and increases transient LES relaxations (TLESRs) in humans. The aims of this study were to determine whether endogenous CCK increases gastroesophageal reflux in humans and whether this is a direct effect on the LES.. Esophageal pH, LES pressure, and gallbladder volume were measured in 8 healthy volunteers after ingestion of a 181-kcal meal alone or adding 12 g cholestyramine to increase endogenous CCK release. In 7 additional volunteers, the effect of cholestyramine was studied during intravenous perfusion of saline or the CCK-A receptor antagonist loxiglumide. In circular LES strips from 9 transplant donors, we measured the effect of CCK-8 (10(-11) to 3 x 10(-8) mol/L) on basal tension and on electrical field-induced relaxation.. Cholestyramine increased gallbladder emptying, reflux episodes, TLESRs, and time of esophageal pH of <4. Loxiglumide inhibited postprandial gallbladder emptying, reflux episodes, TLESRs, and time of pH of <4 and prevented the decrease in LES pressure induced by cholestyramine. In vitro, CCK-8 contracted LES strips through a tetrodotoxin-insensitive pathway but did not modify electrical field-induced LES relaxations.. Endogenous CCK enhances postprandial gastroesophageal reflux in humans by increasing the rate of TLESRs and reduces postprandial LES pressure. These actions seem mediated by extrasphincteric CCK-A receptors that override a direct contractile effect of CCK on the LES muscle.

Topics: Adult; Cholecystokinin; Cholestyramine Resin; Eating; Electric Stimulation; Esophagogastric Junction; Esophagus; Gallbladder; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Male; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Proglumide; Receptor, Cholecystokinin A; Receptors, Cholecystokinin; Sincalide

The effect of cholecystokinin (CCK) on the lower oesophageal sphincter (LOS) pressure, frequency of transient LOS relaxations, and the number of reflux episodes was investigated in six healthy subjects. LOS pressure was recorded on four separate occasions during continuous intravenous infusion of either saline or CCK-33 in doses of 0.25, 0.5, or 1.0 Ivy Dog units per kg body weight per hour (IDU.kg-1.h-1) for 90 minutes. Plasma CCK concentrations did not change during saline infusion, but increased significantly from 2.5 (0.3) pmol/l to steady state levels of 4.0 (0.4) pmol/l, 6.1 (0.4) pmol/l, and 9.3 (0.9) pmol/l respectively starting from 30 minutes. LOS pressure did not change significantly during infusion of saline or of CCK-33 at doses of 0.25 or 0.5 IDU.kg-1.h-1. However, a significant (p < 0.05) reduction in LOS pressure to a minimum level of 12 (4) mm Hg at 30 minutes compared with basal level (18 (4) mm Hg) and compared with saline was observed during infusion of CCK-33 at a dose of 1.0 IDU.kg-1.h-1. In addition, oesophageal motility and pH were recorded simultaneously in these six subjects on two separate occasions one hour before (fasting) and three hours during administration of a gastric load (dextrose 5%, pH 3) combined with continuous intravenous infusion of saline or CCK-33 at a dose of 1.0 IDU,kg-1.h-1. Plasma CCK concentrations did not change during the gastric load combined with saline, but increased significantly to a steady state level of 10.8 (0.8) pmol/l during intravenous infusion of CCK. The number of transient LOS relaxations increased significantly in the first hour during administration of the gastric load compared with fasting levels, both during saline infusion (fasting: 1.7 (0.6)/h, 1st hour: 4.3 (1.2)/h) and during CCK infusion (fasting: 1.7 (0.5)/h, 1st hour: 3.8 (0.7)/h). In the second and third hours the number of transient LOS relaxations fell to fasting levels in both experiments. No significant differences were observed in the number and type of transient LOS relaxations, mechanism of gastro-oesophageal reflux, or duration of acid exposure between the two experiments. It is concluded that in healthy subjects infusion of CCK-33 in a dose of 1.0 IDU.kg-1.h-1 significantly reduces LOS pressure but does not affect the frequency of transient LOS relaxations or acid exposure time during a continuous liquid gastric load.

Topics: Adult; Cholecystokinin; Dose-Response Relationship, Drug; Esophagogastric Junction; Fasting; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Manometry; Muscle Relaxation; Pressure

Topics: Adult; Asthma; Cholecystokinin; Eating; Esophagus; Female; Gastrins; Gastroesophageal Reflux; Gastrointestinal Hormones; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Motilin; Neurotensin; Peristalsis; Somatostatin

The lower oesophageal high pressure zone (HPZ) was studied in 5 non-refluxing and 3 refluxing Rhesus monkeys. The changes in HPZ and reflux status in response to infusion of various doses of secretin, cholecystokinin and glucagon were measured in all animals, and, in the 5 non-refluxing monkeys, after oesophagogastrectomy with replacement of the lower oesophagus by a stomach tube. All three hormones consistently produced a transient decrease in the HPZ pressure. The only change in response following oesophagagastrectomy and gastric tube replacement was a significant delay in the response to each hormone. Neither hormone infusion nor operation altered gastro-oesophageal reflux status. It appears that lower oesophageal competence in primates is more dependent on the presence of narrow, muscular, intra-abdominal tube than on a specialized segment of the lower oesophagus.

Topics: Animals; Cholecystokinin; Esophagogastric Junction; Esophagus; Gastrectomy; Gastroesophageal Reflux; Glucagon; Haplorhini; Macaca mulatta; Male; Pressure; Secretin; Time Factors

Topics: Cardia; Cholecystokinin; Gastrins; Gastroesophageal Reflux; Gastrointestinal Hormones; Gastrointestinal Motility; Humans; Manometry