cholecystokinin and Vomiting

Chronic acalculous gallbladder disease (CAGD) falls within the spectrum of diseases associated with gallbladder dysmotility. Cholecystokinin-cholescintigraphy (CCK-CS) has been used to evaluate for CAGD, with a gallbladder ejection fraction (GBEF) of <35 % being indicative of gallbladder dysfunction. The reproduction of biliary colic upon administration of CCK has been cited as indicative of CAGD. Our purpose was to determine whether low GBEF or reproduction of pain during CCK-CS was predictor of surgical outcomes related to resolution of symptoms or as a correlate to gallbladder pathology.. A retrospective review of patients was performed to evaluate adults with a diagnosis of CAGD who underwent CCK-CS prior to surgical intervention. CPT and ICD-9 coding queries were used to identify the patient population. Patients with cholelithiasis were excluded.. Sixty-four patients met inclusion criteria. Two patients were lost to follow-up and were excluded. During CCK-CS, 41 patients (66 %) reported symptoms similar to their presenting complaint. Twenty-one patients reported no symptoms with CCK-CS. There was no significant relationship between gallbladder pathology and either GBEF or reproduction of symptoms with CCK-CS (p = 0.14). About 81 % of patients (n = 50) had relief of symptoms following cholecystectomy. Sixty-six percentage of patients (n = 33) with long-term symptom relief after cholecystectomy had reproduction of symptoms with CCK-CS. Nineteen percentage of all patients (n = 12) had long-term symptom recurrence despite surgery. Eight of these patients (66 %) had symptom reproduction with CCK-CS. There was no significant correlation with either the GBEF or symptoms reproduction with CCK-CS as a predictor of postoperative outcome (p = 0.12).. Provocation of pain by CCK-CS and low GBEF are unreliable predictors of postoperative relief of symptoms following cholecystectomy for biliary dyskinesia or chronic acalculous gallbladder disease.

Topics: Abdominal Pain; Anorexia; Cholecystectomy; Cholecystokinin; Gallbladder; Gallbladder Diseases; Humans; Nausea; Pain Measurement; Radionuclide Imaging; Vomiting

The mycotoxin deoxynivalenol (DON) elicits robust anorectic and emetic effects in several animal species. However, less is known about the potential for naturally occurring and synthetic congeners of this trichothecene to cause analogous responses. Here we tested the hypothesis that alterations in DON structure found in the plant metabolite deoxynivalenol-3-glucoside (D3G) and two pharmacologically active synthetic DON derivatives, EN139528 and EN139544, differentially impact their potential to evoke food refusal and emesis. In a nocturnal mouse food consumption model, oral administration with DON, D3G, EN139528, or EN139544 at doses from 2.5 to 10 mg/kg BW induced anorectic responses that lasted up to 16, 6, 6, and 3 h, respectively. Anorectic potency rank orders were EN139544>DON>EN139528>D3G from 0 to 0.5 h but DON>D3G>EN139528>EN139544 from 0 to 3 h. Oral exposure to each of the four compounds at a common dose (2.5 mg/kg BW) stimulated plasma elevations of the gut satiety peptides cholecystokinin and to a lesser extent, peptide YY3-36 that corresponded to reduced food consumption. In a mink emesis model, oral administration of increasing doses of the congeners differentially induced emesis, causing marked decreases in latency to emesis with corresponding increases in both the duration and number of emetic events. The minimum emetic doses for DON, EN139528, D3G, and EN139544 were 0.05, 0.5, 2, and 5 mg/kg BW, respectively. Taken together, the results suggest that although all three DON congeners elicited anorectic responses that mimicked DON over a narrow dose range, they were markedly less potent than the parent mycotoxin at inducing emesis.

Topics: Animals; Anorexia; Cholecystokinin; Dose-Response Relationship, Drug; Eating; Female; Glucosides; Intestinal Mucosa; Intestines; Mice, Inbred Strains; Mink; Molecular Structure; No-Observed-Adverse-Effect Level; Peptide Fragments; Peptide YY; Trichothecenes; Vomiting

Deoxynivalenol (DON, vomitoxin), a trichothecene mycotoxin produced by Fusarium sp. that frequently occurs in cereal grains, has been associated with human and animal food poisoning. Although a common hallmark of DON-induced toxicity is the rapid onset of emesis, the mechanisms for this adverse effect are not fully understood. Recently, our laboratory has demonstrated that the mink (Neovison vison) is a suitable small animal model for investigating trichothecene-induced emesis. The goal of this study was to use this model to determine the roles of two gut satiety hormones, peptide YY3-36 (PYY3-36) and cholecystokinin (CCK), and the neurotransmitter 5-hydroxytryptamine (5-HT) in DON-induced emesis. Following ip exposure to DON at 0.1 and 0.25mg/kg bw, emesis induction ensued within 15-30min and then persisted up to 120min. Plasma DON measurement revealed that this emesis period correlated with the rapid distribution and clearance of the toxin. Significant elevations in both plasma PYY3-36 (30-60min) and 5-HT (60min) but not CCK were observed during emesis. Pretreatment with the neuropeptide Y2 receptor antagonist JNJ-31020028 attenuated DON- and PYY-induced emesis, whereas the CCK1 receptor antagonist devezapide did not alter DON's emetic effects. The 5-HT3 receptor antagonist granisetron completely suppressed induction of vomiting by DON and the 5-HT inducer cisplatin. Granisetron pretreatment also partially blocked PYY3-36-induced emesis, suggesting a potential upstream role for this gut satiety hormone in 5-HT release. Taken together, the results suggest that both PYY3-36 and 5-HT play contributory roles in DON-induced emesis.

Topics: Animals; Antiemetics; Benzamides; Cholecystokinin; Devazepide; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Granisetron; Mink; Peptide Fragments; Peptide YY; Piperazines; Serotonin; Serotonin Antagonists; Time Factors; Trichothecenes; Vomiting

Recent data suggest that purging disorder, a recently characterized form of eating disorder not otherwise specified, may be worthy of specific delineation in nosological schemes. However, more data are needed to determine how purging disorder differs from bulimia nervosa.. To examine clinical features and subjective as well as objective physiological responses to a standardized test meal in purging disorder compared with bulimia nervosa and controls.. Study visit 1 included psychological assessments with structured clinical interviews and questionnaires. Study visit 2 included assessment of test-meal responses.. Participants recruited from the community completed test-meal studies in a General Clinical Research Center.. Women with DSM-IV bulimia nervosa-purging subtype (n = 37) and purging disorder (n = 20) and non-eating disorder controls (n = 33) with a body mass index (calculated as weight in kilograms divided by height in meters squared) between 18.5 and 26.5 who were free of psychotropic medications.. Assessments of eating disorder severity, postprandial cholecystokinin response, and subjective responses to test meals.. Eating abnormalities were significantly elevated in participants with purging disorder and bulimia nervosa compared with controls but did not differ between eating disorder groups. Participants with purging disorder demonstrated significantly greater postprandial cholecystokinin release compared with participants with bulimia nervosa (t(76.44) = 2.51; P = .01) and did not differ significantly from controls (t(75.93) = 0.03; P = .98). Participants with purging disorder reported significantly greater postprandial fullness and gastrointestinal distress compared with participants with bulimia nervosa and controls.. Purging disorder is a clinically significant disorder of eating that appears to be distinct from bulimia nervosa on subjective and physiological responses to a test meal. Findings support further consideration of purging disorder for inclusion in the classification of eating disorders. Future studies on the psychobiology of purging disorder are needed to understand the propensity to purge in the absence of binge eating.

Topics: Adult; Appetite; Body Mass Index; Bulimia Nervosa; Cholecystokinin; Control Groups; Diagnosis, Differential; Diagnostic and Statistical Manual of Mental Disorders; Eating; Feeding and Eating Disorders; Female; Humans; Hunger; Personality Inventory; Postprandial Period; Psychiatric Status Rating Scales; Satiation; Severity of Illness Index; Surveys and Questionnaires; Vomiting

Posterior pituitary hormone secretion and central neural expression of the immediate-early gene product c-Fos was examined in adult ferrets after intravenous administration of CCK octapeptide. Pharmacological doses of CCK (1, 5, 10, or 50 microg/kg) did not induce emesis, but elicited behavioral signs of nausea and dose-related increases in plasma vasopressin (AVP) levels without significant increases in plasma oxytocin (OT) levels. CCK activated neuronal c-Fos expression in several brain stem viscerosensory regions, including a dose-related activation of neurons in the dorsal vagal complex (DVC). Activated brain stem neurons included catecholaminergic and glucagon-like peptide-1-positive cells in the DVC and ventrolateral medulla. In the forebrain, activated neurons were prevalent in the paraventricular and supraoptic nuclei of the hypothalamus and also were observed in the central nucleus of the amygdala and bed nucleus of the stria terminalis. Activated hypothalamic neurons included cells that were immunoreactive for AVP, OT, and corticotropin-releasing factor. Comparable patterns of brain stem and forebrain c-Fos activation were observed in ferrets after intraperitoneal injection of lithium chloride (LiCl; 86 mg/kg), a classic emetic agent. However, LiCl activated more neurons in the area postrema and fewer neurons in the nucleus of the solitary tract compared with CCK. Together with results from previous studies in rodents, our findings support the view that nauseogenic treatments activate similar central neural circuits in emetic and nonemetic species, despite differences in treatment-induced emesis and pituitary hormone secretion.

Topics: Animals; Arginine Vasopressin; Behavior, Animal; Brain Stem; Cell Count; Cholecystokinin; Dose-Response Relationship, Drug; Ferrets; Glucagon; Glucagon-Like Peptide 1; Infusions, Intravenous; Injections, Intraperitoneal; Lithium Chloride; Male; Neurons; Organ Specificity; Oxytocin; Peptide Fragments; Pituitary Hormones, Posterior; Prosencephalon; Protein Precursors; Proto-Oncogene Proteins c-fos; Vomiting

Topics: Animals; Bile; Bile Ducts, Extrahepatic; Cholecystokinin; Dogs; Gallbladder; Gastrins; Movement; Sphincter of Oddi; Vomiting

1. A transient increase in plasma vasopressin concentrations represents a physiological correlate of nausea in animals that vomit. 2. The CCKA receptor antagonist devazepide has previously been shown to inhibit vasopressin release induced in pigs by intravenous (i.v.) CCK. 3. This study investigated whether devazepide (70 micrograms/kg i.v.) would affect vasopressin secretion induced in pigs (n = 6) by the emetic drug apomorphine (25 micrograms/kg i.v.). 4. Apomorphine stimulated vasopressin release in the 30 min period following injection; this effect was prevented by prior administration of devazepide. 5. The results suggest that CCKA receptor antagonists may have the ability to prevent nausea and/or emesis.

Topics: Animals; Apomorphine; Benzodiazepinones; Cholecystokinin; Devazepide; Drug Interactions; Lypressin; Nausea; Receptors, Cholecystokinin; Swine; Vomiting

There is evidence to suggest that the arginine vasopressin release observed in association with emesis after i.v. injection of cholecystokinin (CCK) and N-methyl-D-aspartate (NMDA) is mediated by stimulation of emetic centers in the brainstem. That the GnRH-releasing action of NMDA is also sometimes accompanied by emesis led to the suggestion that stimulation of this parvocellular system by the glutamate agonist may also be mediated in part via activation of brainstem pathways. If this is the case, then other nauseogenic agents, such as CCK, should similarly elicit GnRH release. The foregoing prediction was tested in the castrated juvenile male monkey, an experimental model characterized by the absence of spontaneous GnRH release. GnRH discharges were monitored indirectly by measuring changes in circulating LH concentrations after the responsivity of the gonadotroph had been heightened by a chronic intermittent i.v. infusion of the decapeptide. An i.v. bolus of CCK at 10 and 30 micrograms/kg BW led to a distinct discharge of GnRH accompanied by emesis or other behaviors suggestive of nausea. Lower doses of CCK (1 and 3 micrograms/kg BW) failed to significantly perturb GnRH release or cause emesis, although NMDA (5 mg/kg BW; racemic form) injected i.v. 3 h after the CCK challenge led to a robust rise in GnRH. In a parallel study, three repetitive i.v. CCK injections at 2h intervals maintained intermittent GnRH release. Pretreatment with a long-acting GnRH receptor antagonist ([AcD2Nal1,4ClPhe2,DTrp3,DArg6,DAla10]GnRH -HOAc) abolished the LH response to CCK, confirming that the action of this peptide was mediated by GnRH release. Although a direct hypothalamic site of action for these agents remains the most likely possibility, since both NMDA and CCK receptors are present in the infundibular region, the present data are consistent with the notion that CCK and, by inference, NMDA may activate GnRH release in part via the stimulation of brainstem emetic centers. Plasma GH, PRL, and cortisol concentrations were also monitored during the course of some of these experiments, and the release of these hormones was observed after the administration of either the 10 or 30 micrograms/kg BW dose of CCK.

Topics: Animals; Cholecystokinin; Gonadotropin-Releasing Hormone; Growth Hormone; Hydrocortisone; Injections, Intravenous; Luteinizing Hormone; Macaca mulatta; Male; Pituitary Gland; Prolactin; Vomiting

Administration of lithium chloride and copper sulfate to adult monkeys caused marked elevations in plasma vasopressin (AVP) levels without significant increases in plasma oxytocin (OT) levels. Emesis was produced in five of the seven animals given these agents, in support of nausea as the main stimulus to AVP release. A similar pattern of AVP release without OT release was found after administration of cholecystokinin (CCK). Although most monkeys vomited in response to 10 micrograms/kg of CCK, a significant increase in plasma AVP levels also was produced with a dose of 1 microgram/kg, which did not produce emesis in any animal. These findings are in marked contrast with previous results in rats, which indicated that lithium chloride, copper sulfate, and CCK each stimulated OT rather than AVP release. Despite this interspecies difference, the significant neurohypophysial hormone secretion in response to both nausea-producing agents and CCK suggests that AVP secretion in monkeys, similar to OT secretion in rats, might reflect activation of central pathways mediating nausea and/or inhibition of food intake, even when overt illness is not produced.

Topics: Animals; Arginine Vasopressin; Chlorides; Cholecystokinin; Copper; Copper Sulfate; Haplorhini; Lithium; Lithium Chloride; Nausea; Oxytocin; Rats; Vomiting

Topics: Adult; Age Factors; Biliary Tract Diseases; Cholecystectomy; Cholecystography; Cholecystokinin; Cholelithiasis; Colic; Cystic Duct; Female; Humans; Middle Aged; Nausea; Psychophysiologic Disorders; Sex Factors; Vomiting

1. In the intact conscious dog, caerulein causes emesis and evacuation of the bowel. The mean effective dose by the intravenous route is 0.4-0.5 mug/kg, and by the subcutaneous route 3-4 mug/kg.2. The gall bladder in situ or as an isolated preparation is highly sensitive to caerulein. A few ng/kg injected intravenously are sufficient to stimulate the gall bladder in situ and less than 1 ng/kg per min is effective when infused intravenously. The isolated gall bladder is contracted by caerulein in concentrations as low as 0.03-2 ng/ml. Krebs solution. There is no tachyphylaxis but, generally, a good dose-response relationship. Hence the gall bladder, especially that of the guinea-pig, appears to be very suitable for the bioassay of caerulein and related peptides.3. In situ, the musculature of the gastrointestinal tract is also highly sensitive to caerulein. Doses as low as 1-5 ng/kg, administered intravenously, have a spasmogenic action on jejunal loops of the dog, and slightly larger doses contract the small intestine of the cat. The stomach and the large intestine seem to be somewhat less sensitive to the polypeptide. Caerulein has a considerable spasmogenic action on the rat pylorus but relaxes the sphincter of Oddi of the guinea-pig.4. Isolated preparations of the gastrointestinal tract are relatively insensitive to caerulein and tachyphylaxis occurs readily.5. Blockade with atropine produces different effects in different intestinal segments and in different animal species. The spasmogenic action of caerulein on the gall bladder is atropine-resistant.6. The effects of caerulein are similar to those of cholecystokinin-pancreozymin in the organs tested in situ or as isolated preparations. Caerulein, however, is always more potent than cholecystokinin-pancreozymin, even on a molar basis. Compared with caerulein, human gastrin I has negligible activity.7. The possible use of caerulein in cholecystography is discussed.

Topics: Animals; Atropine; Biological Assay; Cholecystography; Cholecystokinin; Digestive System; Dogs; Gallbladder; Jejunum; Muscle, Smooth; Peptides; Tachyphylaxis; Vomiting