Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Octreotide is a long-acting cyclic octapeptide with pharmacologic actions mimicking those of the natural hormone somatostatin. It can suppress the secretion of serotonin, as well as the gastroenteropancreatic peptides gastrin, vasoactive intestinal peptide (VIP), insulin, glucagon, secretin, motilin, and pancreatic polypeptide. It also suppresses growth hormone and decreases splanchnic blood flow. Octreotide is completely and rapidly absorbed following subcutaneous injection and has an elimination half-life of 1.5 hours. Clinical trials reviewed here show octreotide useful in the treatment of diarrhea associated with VIP secreting tumors, as well as diarrhea and flushing associated with carcinoid syndrome, both conditions for which the drug is approved. Clinical trials involving the use of octreotide in the treatment of acromegaly are also reviewed. Adverse reactions to octreotide are mild to moderate and most commonly involve injection site pain and diarrhea. Drug interactions are apparently related to the drug's pharmacologic effects. Octreotide is given subcutaneously two to three times daily, with daily doses ranging from 50mcg to 1,500mcg per day. Further research appears necessary to clarify dosing issues.
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PMID:Debut of a somatostatin analog: octreotide in review. 255 39

A 59-year-old female presented with multifocal peptic ulcer disease and diarrhea. A fasting serum gastrin level obtained while the patient was receiving no antacid therapy was normal. A secretin stimulation test was positive. A small gastrinoma was found in the anterior duodenal wall at exploratory laparotomy. Normal fasting gastrin levels do occur in patients with overt Zollinger-Ellison syndrome and should not deter further investigation if clinical suspicion of this syndrome is high.
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PMID:Zollinger-Ellison syndrome in a patient with normal screening gastrin level. 259 59

In this study, the pharmacokinetics, efficacy, and tolerability of 25 and 100 micrograms of octreotide given t.i.d. for 7 days subcutaneously were investigated in 12 healthy male subjects. Serum concentrations of the drug were well reproducible within 1 wk. Octreotide significantly raised 24-h median intragastric pH on day 1, but no longer on day 6. Peptone-stimulated gastric acid and volume secretion were markedly less suppressed by octreotide on day 7 compared with day 2. Peptone-stimulated gastrin release was abolished on days 2 and 7, as was peptone-stimulated insulin release. Blood glucose was altered in a biphasic pattern on days 2 and 7. All effects of octreotide were without clear-cut dose-response relationship. A mean half-life of 115 min was calculated. Dose-unrelated side effects (e.g., abdominal cramps, diarrhea, and fatty stools) were registered. In conclusion, octreotide is a powerful inhibitor of gastric acid and volume secretion during acute treatment. Its loss of efficacy during a 1-wk administration may be due to the adaptation of somatostatin receptors and hormonal counterregulation.
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PMID:Diminishing efficacy of octreotide (SMS 201-995) on gastric functions of healthy subjects during one-week administration. 264 51

A 36-yr-old man was admitted to our hospital complaining of severe vomiting and diarrhea. Upper gastrointestinal series showed deformity of the duodenum. Serum gastrin level was very high (1,829 pg/ml) and secretin provocative test presented a positive result (peak 4,535 pg/ml). We diagnosed his illness as Zollinger-Ellison syndrome, but failed to identify the site of tumor. His symptoms were controlled with cimetidine 1,600 mg qid, but serum gastrin level was increasing. A year after the first admission, computed tomographic scan and selective angiography demonstrated the tumor, and surgery was performed. A solitary 2-cm tumor was noted at the surface of mesenterium of the duodenum. Frozen and paraffin section of the tumor revealed islet cell tumor apparently within a lymph node. Immunohistological examination revealed positive staining for gastrin alone. No other tumors were detectable by inspection and palpation during the operation. After excision of the tumor, serum gastrin and secretion test were normalized, and the patient remains asymptomatic 1 yr after surgery.
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PMID:Gastrinoma in a mesenteric lymph node. 265 53

Among 30 patients with islet cell neoplasms or hyperplasia who exhibited marked gastric acid hypersecretion and peptic ulceration and/or diarrhea, fasting plasma gastrin concentrations were less than 150 pg/ml in 11 patients, whereas the remaining 19 patients had hypergastrinemia. Plasma extracts from seven of these 11 patients were assayed for acid secretagogue activity in rats. All seven plasma extracts had secretagogue activity that was not found in the plasma extracts of ten patients with ordinary duodenal ulcer disease. Each of the tumor or pancreatic tissue extracts obtained from nine patients exhibited secretagogue activity in rats even though tissue gastrin content was 101.9 pmol (213.8 ng).g-1 or less. The secretagogue activity of the tumor extracts was confirmed in conscious gastric fistula dogs. The tumors' secretagogue activity, in contrast to gastrin, was destroyed by trypsin. It was eluted between porcine motilin and human gastrin I from a Sephadex G-50 (Pharmacia LKB Biotechnology, Inc., Piscataway, NJ) superfine column and was not retained by CM-cellulose, at pH 8.5. Its retention time during reverse phase HPLC on a C18 column also differed from those of G17 and G34. Thus, this secretagogue activity appeared mediated by a small, acidic peptide with a molecular size of about 2000 to 3000 daltons. The present study indicates that plasma and tumor extracts of these 11 patients contain a gastric acid secretagogue activity mediated by a nongastrin peptide. We suggest that what may be a distinct clinical entity associated with endocrine neoplasms of the pancreas should be considered in the face of excessive acid hypersecretion without fasting hypergastrinemia.
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PMID:Ulcerogenic tumor syndrome of the pancreas associated with a nongastrin acid secretagogue. 275 18

Omeprazole efficacy and tolerance were evaluated in 20 patients with longstanding Zollinger-Ellison syndrome (ZES) committed to long-term antisecretory therapy. The study included 13 men and 7 women, aged 53 (30-74) years (median and range). Nineteen patients presented with epigastric pain, 14 with vomiting, and 9 with diarrhea. All patients had gastroduodenal ulcerations, associated with esophagitis in 9 cases. Median and extreme values for basal acid output (BAO) and serum gastrin (SG) levels before omeprazole treatment were 41 (3.7-80) mmol H+/h and 413 (111-11,490) pg/ml, respectively. In 18 patients, omeprazole treatment was initiated because of resistance to H2-antagonists, and in 2 patients because of carbothioamide RP 40749 discontinuation. Initial doses of omeprazole were 60 mg per day in 10 patients and ranged from 80 to 160 mg per day in the others. Esophagogastrectomy was performed in one patient at day 15 because of esophageal stenosis. In the remaining 19 patients, median duration of treatment was 16 (7-54) months and median doses of omeprazole were 70 (20-160) mg per day during the survey. Omeprazole therapy was highly effective in inducing rapid disappearance of clinical abnormalities in 18 of 19 patients. Twenty-two days after initiation of treatment, median BAO was 4 (0-14) mmol/h and ulcerations had healed in 17 of 19 patients. Median BAO was less than 5 mmol/h during follow-up. However, asymptomatic ulcer recurrence was noted in 4 patients, but disappeared quickly after omeprazole doses were increased. Median basal gastrin level was 700 (116-36.625) pg/ml at the least determination and was statistically higher than pretreatment values (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Long-term efficacy and tolerability of omeprazole in 20 patients with severe Zollinger-Ellison syndrome]. 280 1

The long-acting somatostatin analogue SMS 201-995 was administered to a six-month-old infant with intractable diarrhea after failure of conventional treatment. During eight weeks of treatment, the secretory component of the diarrhea was positively influenced with a reduction of daily stool weight and stool sodium concentration. Plasma levels of growth hormone were markedly, and levels of insulin, IGF I, gastrin, pancreatic polypeptide, VIP, and neurotensin moderately decreased. Linear growth was also inhibited. The patient unexpectedly died from fulminant colitis at a time, when the dosage had been reduced from 18 to 3.5 micrograms/kg/day. The relationship, if any, between therapy with SMS 201-995 and the colitis remained unclear. It is concluded that SMS 201-995 can be effective in reducing secretory diarrhea in infants. However, further studies are necessary to assess the safety of its administration in this age group.
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PMID:Effects of the long-acting somatostatin analogue SMS 201-995 in an infant with intractable diarrhea. 284 5

A 30-year-old man presenting with watery diarrhea, hypokalemia, and hypochlorhydria (Verner-Morrison syndrome, WDHH syndrome) had raised plasma levels of vasoactive intestinal polypeptide (VIP), somatostatin (SRIF), calcitonin, and gastrin, as well as high urinary excretion of vanillylmandelic acid. A right adrenal pheochromocytoma was found and excised. The neoplastic cell population was immunohistochemically shown to contain VIP, SRIF, and calcitonin. Gross, histologic, and immunohistochemical evaluation of the pancreas revealed no abnormalities, whereas a marked hyperplasia of the gastrin-producing cells of the gastric antral mucosa was demonstrated. Postoperatively, the patient recovered from his symptoms and the plasma hormone levels returned to normal values. The clinical and histogenetic implications of this most unusual tumor of neural crest derivatives are discussed.
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PMID:Vasoactive intestinal polypeptide-, somatostatin-, and calcitonin-producing adrenal pheochromocytoma associated with the watery diarrhea (WDHH) syndrome. First case report with immunohistochemical findings. 285 7

A case of carcinoid tumor of the pancreas with the watery diarrhea, hypokalemia, and hypochlorhydria syndrome in association with hyperparathyroidism and the amenorrhea-galactorrhea syndrome is presented. Resection of the three grossly enlarged, hyperplastic parathyroid glands restored eucalcemia in this patient. A subsequent excision of the 370 gm pancreatic carcinoid tumor resulted in a cure of the watery diarrhea and a return of the gastric acid secretion to normal. Immunocytochemical studies of the pancreatic tumor demonstrated a positive stain only for serotonin, and negative results for vasoactive intestinal polypeptide, pancreatic polypeptide, glucagon, insulin, cholecystokinin, gastrin, and calcitonin were obtained. These studies suggest that in this patient, serotonin was a causative agent of the watery diarrhea syndrome.
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PMID:Carcinoid tumor of the pancreas causing the diarrheogenic syndrome: report of a case combined with multiple endocrine neoplasia, type I. 286 11

The effects of various biologically active peptides on net jejunal water and electrolyte fluxes were studied in dogs in vivo. Vasoactive intestinal peptide (VIP), gastric inhibitory polypeptide (GIP), glucagon, gastrin, bombesin and neurotensin all had secretagogue activity, while methionine enkephalin stimulated net absorption. Somatostatin had no effect on net basal water and electrolyte transport, but inhibited glucagon-stimulated secretion. Secretin, calcitonin, substance P and pancreatic polypeptide (PP) did not have any effect on net water and electrolyte transport in the doses used in these experiments. The precise role played by these peptides in the control of intestinal transport has still to be determined. Studies in man have confirmed that food in the proximal small bowel stimulates secretion at sites remote from the application of food, and abnormal secretion of some peptides (e.g. VIP) has been associated with diarrhoea. Somatostatin has been used successfully to reduce the volume of certain types of secretory diarrhoea. Methods used in these experiments have been applied to the study of the composition and absorption characteristics of solutions used for oral rehydration in diarrhoea and in exercise-induced dehydration. Glucose polymers have been shown to be absorbed as rapidly as glucose from the jejunum.
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PMID:The effect of luminal and hormonal factors on small intestinal water and electrolyte transport. 287 15


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