cholecystokinin and Zollinger-Ellison-Syndrome

Topics: Adenoma, Islet Cell; Cholecystokinin; Digestive System Diseases; Gastrointestinal Hormones; Glucagon; Glucagonoma; Humans; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Pancreatic Polypeptide; Somatostatin; Somatostatinoma; Vipoma; Zollinger-Ellison Syndrome

Gastrointestinal hormones are chemical messengers that regulate a broad range of physiologic functions. Although primarily expressed within tissues of the gut, these peptide hormones are widely distributed throughout the body and act on multiple target tissues. Furthermore, these regulatory peptides can exist in multiple molecular forms that may bind to multiple cell-surface receptors coupled to one of several possible signal transduction systems leading to diverse biologic responses. With such an expansive field to study, it is not surprising that gut endocrinologists have embraced the new techniques that are emerging from the revolution of molecular biology. Beginning with the first construction of a recombinant DNA molecule by Paul Berg in 1971, molecular biology has developed many new techniques that have been rapidly adopted by gut endocrinologists to enable a more detailed understanding of gastrointestinal function. The merging of these two fields has led to a new area of research, molecular gut endocrinology, or the study of gut physiology and endocrinology at the level of individual molecules (ranging from polypeptide-surface receptors to small-molecule second messengers to DNA sequences). Gut cells are constantly bombarded by numerous hormones, and the tightly regulated physiologic status of each cell is becoming more clearly understood.

Topics: Animals; Cholecystokinin; Digestive System Physiological Phenomena; Dogs; Endocrinology; Gastrins; Humans; Molecular Biology; Radioimmunoassay; Rats; Receptors, Cholecystokinin; Signal Transduction; Tumor Cells, Cultured; Zollinger-Ellison Syndrome

Topics: Animals; Cholecystokinin; Diagnostic Errors; Dogs; Duodenal Ulcer; Eating; Fasting; Guinea Pigs; Haplorhini; Hormones; Humans; Iodine Radioisotopes; Rabbits; Radioimmunoassay; Rats; Reference Standards; Secretin; Swine; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Chenodeoxycholic Acid; Cholecystokinin; Cholelithiasis; Dehydration; Diabetes Mellitus; Duodenal Ulcer; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Motilin; Pancreatic Neoplasms; Secretin; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Bombesin; Cholecystokinin; Cimetidine; Epidermal Growth Factor; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Motilin; Nerve Tissue; Pancreas; Pancreatic Polypeptide; Pituitary Gland; Secretin; Somatostatin; Stomach Neoplasms; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Cholecystokinin; Gastric Juice; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Neoplasms; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Peptides; Precancerous Conditions; Secretin; Somatostatin; Stomach Neoplasms; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Animals; Cholecystokinin; Dogs; Gastric Inhibitory Polypeptide; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Pancreatic Diseases; Radioimmunoassay; Secretin; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Animals; Cholecystokinin; Dogs; Feedback; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Secretin; Swine; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Animals; Cholecystokinin; Esophageal Achalasia; Esophagogastric Junction; Esophagus; Estradiol; Gastric Juice; Gastrins; Glucagon; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Opossums; Pressure; Progesterone; Secretin; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Cholecystokinin; Diarrhea; Gastrins; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Glucagon; Hormones, Ectopic; Humans; Insulin; Insulin Secretion; Neurosecretory Systems; Pancreatic Hormones; Paraneoplastic Endocrine Syndromes; Prostaglandins; Serotonin; Syndrome; Vasoactive Intestinal Peptide; Werner Syndrome; Zollinger-Ellison Syndrome

There is evidence that under various physiological circumstances long-term adaptation of structure and function of the gut occurs. The mechanisms of these changes are not clear but gastro-intestinal hormones may be involved. In particular, gastrin which has been shown experimentally to stimulate growth and development of parts of the gut, probably has a role in maintaining the structure of the normal upper alimentary tract. Cholecystokinin may be of major importance in producing adaptive changes in the pancreas in response to dietary modifications and enteroglucagon is possibly concerned with maintaining a normal small intestinal structure. The importance of the 'trophic' action of gatrointestinal hormones is becoming more widely recognised and as new gastro-intestinal hormones become established, this aspect of their physiological importance as well as their acute effects, will deserve attention.

Topics: Animals; Cholecystokinin; DNA; Duodenum; Female; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Humans; Intestinal Diseases; Intestine, Small; Kidney Failure, Chronic; Lactation; Pancreas; Pregnancy; Rats; Secretin; Starvation; Weaning; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Acute Kidney Injury; Adenoma, Islet Cell; Adult; Cholecystokinin; Dehydration; Diarrhea; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Hypercalcemia; Hypokalemia; Kidney Diseases; Male; Pancreatic Neoplasms; Protein Precursors; Secretin; Syndrome; Zollinger-Ellison Syndrome

Topics: Cholecystokinin; Duodenal Ulcer; Duodenum; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Hypertrophy; Intestinal Mucosa; Pepsin A; Secretory Rate; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Animals; Cholecystokinin; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Insulin; Insulin Secretion; Intestinal Mucosa; Pancreatic Hormones; Peptides; Secretin; Zollinger-Ellison Syndrome

Topics: Animals; Cholecystokinin; Dogs; Duodenal Ulcer; Esophagus; Gallbladder; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Pancreatic Juice; Secretin; Secretory Rate; Stimulation, Chemical; Stomach Ulcer; Vagotomy; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Amino Acid Sequence; Animals; Cholecystokinin; Dogs; Duodenum; Fluorescent Antibody Technique; Gastrins; Gastrointestinal Hormones; Humans; Insulin; Insulin Secretion; Intestinal Mucosa; Peptides; Radioimmunoassay; Secretin; Zollinger-Ellison Syndrome

Topics: Age Factors; Anemia, Pernicious; Antigen-Antibody Reactions; Antigens, Neoplasm; Cholecystokinin; Cross Reactions; Digestive System Physiological Phenomena; Duodenal Ulcer; Gastric Mucosa; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Glucagon; Hepatitis B Antigens; Hormones; Humans; Hyperglycemia; Insulin; Methods; Radioimmunoassay; Secretin; Zollinger-Ellison Syndrome

Topics: Celiac Disease; Cholecystokinin; Digestion; Gastrins; Gastrointestinal Hormones; Homeostasis; Humans; Postgastrectomy Syndromes; Secretin; Vagotomy; Zollinger-Ellison Syndrome

Topics: Acute Disease; Adenoma, Islet Cell; Cholecystokinin; Chronic Disease; Gastrins; Humans; Methods; Pancreas; Pancreas Transplantation; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Radiography; Secretin; Transplantation, Homologous; Zollinger-Ellison Syndrome

Topics: Animals; Antibodies; Antibody Formation; Cholecystokinin; Cross Reactions; Gastrins; Guinea Pigs; Humans; Rabbits; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Animals; Cholecystokinin; Chromogranin A; Diagnosis, Differential; Fatal Outcome; Female; Gastrins; Humans; Liver; Liver Neoplasms; Middle Aged; Neuroendocrine Tumors; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Topics: Cholecystokinin; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hormones; Humans; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Using fragment 5-17 of human gastrin-17 extended with glycine at the C-terminus as hapten, three of six rabbits produced high-titer, high-avidity antisera specific for glycine-extended gastrins. In combination with trypsin and carboxypeptidase B cleavage, radioimmunoassays based on these antisera measured progastrins in some extra-antral tissues and certain malignant tumors. The results show that sequential cleavage with trypsin and carboxypeptidase B followed by radioimmunoassay of glycine-extended peptides is a rapid and accurate procedure for measurement of biosynthetic precursors of alpha-amidated peptide hormones. Moreover, the procedure seems promising in the search for tumor markers.

Topics: Animals; Carboxypeptidase B; Carboxypeptidases; Cholecystokinin; Chromatography, Gel; Chromatography, Ion Exchange; Gastrins; Glycine; Hormones; Humans; Hydrolysis; Protein Precursors; Radioimmunoassay; Swine; Trypsin; Zollinger-Ellison Syndrome

We examined the specificity of commercially available antibodies used in measurement of serum gastrin. Antibodies were obtained from five commercial laboratories, and antibody immunoreactivity with gastrin and cross-reactivity with cholecystokinin (CCK) were determined. All antibodies were equally immunoreactive with gastrin, and cross-reactivity of three antibodies with CCK was minimal (less than 5%). In contrast, substantial cross-reactivity with CCK was found with two antibodies. To determine the clinical significance of cross-reactivity with CCK, secretin injection tests were performed in 24 individuals: seven in normal health, four with Zollinger-Ellison syndrome, three with antral gastrin cell hyperfunction, six with ordinary duodenal ulcer disease, and four with atrophic gastritis. Serum gastrin levels were measured with all five gastrin antibodies. The response to secretin was negative in all normal subjects and in those with duodenal ulcer and antral gastrin cell hyperfunction. The response to secretin was positive in all four patients with gastrinoma with use of the five antisera. All four patients with atrophic gastritis had normal responses to secretin when antibodies with minimal CCK cross-reactivity were used; however, two of four had false positive secretin test results when serum gastrin levels were measured with the two antibodies with a high degree of cross-reactivity with CCK. These studies indicate that significant cross-reactivity of gastrin antibodies with CCK can result in false positive secretin injection test results and can lead potentially to the erroneous diagnosis of Zollinger-Ellison syndrome.

Topics: Antibodies; Cholecystokinin; Cross Reactions; False Positive Reactions; Gastrins; Gastrointestinal Diseases; Humans; Injections, Intravenous; Radioimmunoassay; Secretin; Structure-Activity Relationship; Zollinger-Ellison Syndrome

Topics: Acute Disease; Adenocarcinoma; Carcinoma; Cholangiopancreatography, Endoscopic Retrograde; Cholecystokinin; Chronic Disease; Humans; Insulinoma; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Secretin; Time Factors; Zollinger-Ellison Syndrome

Topics: Amino Acid Sequence; Animals; Brain Chemistry; Cholecystokinin; Dogs; Gastric Acid; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Swine; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Pancreas and gut hormones are involved in many endocrine and gastrointestinal diseases. Radioimmunoassays for these hormones have proved particularly valuable in diagnosis, localisation and control of treatment of endocrine tumours, of which many are mixed. An estimate based on ten years experience in a homogenous population of 5 million inhabitants (Denmark) suggests, that endocrine gut tumour-syndromes on an average appear with an incidence of 1 patient per year/syndrome/million. At present six different syndromes are known: 1) The insulinoma syndrome, 2) The Zollinger-Ellison syndrome.3) The Verner-Morrison syndrome. 4) The glucagonoma syndrome. 5) The somatostatinoma syndrome, and 6) the carcinoid syndrome. Accordingly diagnostically valuable RIAs for pancreas and gut hormones include those for insulin, gastrin, VIP, HPP, glucagon, somatostatin, and presumably also substance P. It is probably safe to predict that the need for gut and pancreas hormone RIAs within the next decade will increase greatly in order to assure proper management of tumours producing gastroentero-pancreatic hormones.

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Cholecystokinin; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Insulin; Intestinal Neoplasms; Motilin; Pancreatic Hormones; Pancreatic Neoplasms; Pancreatic Polypeptide; Radioimmunoassay; Secretin; Somatostatin; Substance P; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Gastro-entero-pancreatic (GEP) and bronchial endocrine tumours have been studied by immunohistochemistry using specific antisera against a variety of hormonal and neuronal peptides. In gastrinomas numerous tumour cells were found to contain GH-like immunoreactivity. These cells were identical with those storing gastrin. Gastrinomas as a rule were extremely heterogeneous containing a variety of minority cell populations, including CCK immunoreactive cells and neurotensin immunoreactive cells. Glucagonoma cells were found to store GIP-like material in addition to glucagon. In some insulinomas calcitonin-like material was encountered in the insulin producing tumour cells. In both glucagonomas and insulinomas other pancreatic endocrine cell types constituted minority cell populations. One intestinal somatostatinoma contained gastrin cells as a minority cell population. Bronchial endocrine tumours contained scattered cells displaying ACTH-like or enkephalin-like immunoreactivity. Two such tumours in addition contained cells displaying neurophysin immunoreactivity.

Topics: Adenoma, Islet Cell; Adrenocorticotropic Hormone; Bronchial Neoplasms; Cholecystokinin; Enkephalins; Fluorescent Antibody Technique; Gastrins; Glucagon; Growth Hormone; Humans; Insulin; Insulin Secretion; Neurophysins; Pancreatic Neoplasms; Serotonin; Somatostatin; Stomach Neoplasms; Zollinger-Ellison Syndrome

Topics: Cholecystokinin; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Peptides; Secretin; Somatostatin; Zollinger-Ellison Syndrome

The availability of pure intestinal hormones and the development of radioimmunoassays for their measurement has expedited research into many aspects of gastrointestinal endocrinology. A complex balance evidently exists between the different intestinal hormones and also the rest of the endocrine system. Polyendocrinopathies have been described, and, so far, two diseases due to intestinal hormone excess (Zollinger-Ellison syndrome and the syndrome of watery diarrhea, hypokalemia and achlorhydria) elucidated. It seems likely that many more gastrointestinal endocrine diseases await discovery.

Topics: Cholecystokinin; Diagnosis, Differential; Diarrhea; Digestive System; Endocrine Glands; Esophagogastric Junction; Gastrins; Gastrointestinal Hormones; Humans; Hypoglycemia; Intestinal Diseases; Intestine, Large; Pancreas; Peptic Ulcer; Prostaglandins; Pylorus; Secretin; Syndrome; Zollinger-Ellison Syndrome

Present knowledge about gastrointestinal peptide hormones is discussed from three points of view: (a) diagnostic significance of these hormones; (b) states characterized by over-production or deficiency of peptide hormones; (c) clinical application and perspectives of gastrointestinal hormones. The data in the literature are subjected to a critical analysis; in addition, the author's own experiments are discussed.

Topics: Anemia, Pernicious; Celiac Disease; Cholecystokinin; Duodenal Ulcer; Duodenum; Esophageal Diseases; Gastrins; Gastrointestinal Hormones; Humans; Peristalsis; Pyloric Stenosis; Secretin; Spasm; Zollinger-Ellison Syndrome

Topics: Cholecystokinin; Gastrins; Gastrointestinal Hormones; Humans; Radioimmunoassay; Zollinger-Ellison Syndrome

We have developed a sensitive, specific and reproducible radioimmunoassay for cholecystokinin (CCK) with which basal levels of CCK of between 400-800 pg/ml have been measured in normal man, in patients with diabetes and with duodenal ulcer disease, and in normal dogs. After a meal, circulating levels of CCK rose to 1000-1200 pg/ml in human subjects. Release of CCK was more rapid in diabetic and duodenal ulcer patients than in normal subjects, but elevated postprandial levels persisted much longer in normal subjects. Patients with the Zollinger-Ellison syndrome had elevated values of cholecystokinin which rose after a meal. Lack of correlation between elevated basal levels of gastrin and CCK in patients with the Zollinger-Ellison syndrome suggest that the hypercholecystokininemia may be absolute. The disappearance half-time of exogenous CCK was about 21/2 minutes in normal subjects as well as in diabetic and duodenal ulcer patients. Studies in dogs demonstrated no uptake of basal levels of cholecystokinin by the kidney; on infusion of exogenous CCK-33, the kidney extracted 43% of the total CCK presented and 56% of the integrated CCK. We conclude that: 1) circulating basal and postprandial levels of CCK may be measured in a reproducible fashion; 2) postprandial release of CCK is more rapid in diabetic and duodenal ulcer patients than in normal man; 3) the disappearance half-time of exogenous CCK in man and dogs is about 21/2 minutes; 4) the kidney is a major site for uptake of CCK.

Topics: Animals; Cholecystokinin; Diabetes Mellitus; Dogs; Duodenal Ulcer; Food; Gastrins; Half-Life; Humans; Kidney; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Cholecystokinin; Digestive System; Duodenal Ulcer; Endocrine Glands; Gastrins; Gastrointestinal Hormones; Hormones, Ectopic; Humans; Paraneoplastic Endocrine Syndromes; Secretin; Zollinger-Ellison Syndrome

Topics: Animals; Cholecystokinin; Duodenal Ulcer; Eating; Electric Stimulation; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Hydrogen-Ion Concentration; Parasympatholytics; Peptic Ulcer; Pyloric Antrum; Radioimmunoassay; Secretin; Secretory Rate; Stomach Ulcer; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Bicarbonates; Cholecystokinin; Depression, Chemical; Duodenum; Gastrectomy; Gastric Juice; Gastrins; Humans; Intestinal Secretions; Male; Middle Aged; Secretin; Secretory Rate; Stimulation, Chemical; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Animals; Cholecystokinin; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hormones; Hyperparathyroidism; Pancreas; Rats; Secretin; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Animals; Cholecystokinin; Chromatography, Gel; Electrophoresis; Gastrins; Guinea Pigs; Humans; Iodine Isotopes; Ion Exchange; Methods; Radioimmunoassay; Swine; Zollinger-Ellison Syndrome

Topics: Animals; Antibodies; Buffers; Cholecystokinin; Gastrins; Humans; Immune Sera; Methods; Radioimmunoassay; Swine; Zollinger-Ellison Syndrome

Topics: Age Factors; Animals; Antibody Formation; Blood Protein Electrophoresis; Blood Proteins; Chickens; Cholecystokinin; gamma-Globulins; Gastric Juice; Gastrins; Humans; Immune Sera; Immunization; Immunodiffusion; Iodine Isotopes; Peptides; Precipitin Tests; Protein Binding; Radioimmunoassay; Rats; Swine; Zollinger-Ellison Syndrome

Topics: Animals; Antigens; Cholecystokinin; Digestive System Physiological Phenomena; Gastrins; Humans; Iodine Isotopes; Peptides; Rabbits; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Cholecystokinin; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Secretin; Stomach; Zollinger-Ellison Syndrome