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)

Cathepsin-D has been previously reported to cleave intact PTH into PTH-(1-34) and -(35-84) in membranous fractions of rat and bovine kidney. Whether PTH degradation occurs by intact kidney cells, however, has not been examined in detail. We have, therefore, examined this possibility using an opossum kidney (OK) cell line which possesses the characteristics of proximal renal tubules and responds to PTH. PTH radioimmunoreactivity recovered in trichloroacetic acid-soluble products and in fractions eluted from reverse phase HPLC was measured using an antibody directed to the midregion and C-terminus of PTH. In this study, intact OK cells, but not extracellular enzymes, cleaved human (h) PTH-(1-84) into three discrete fragments which were released into the medium in a time- and temperature-dependent fashion. Half-maximal velocity of PTH-degrading activity (PTHDA) was observed at 9 nM hPTH-(1-84). A 1000-fold molar excess of PTH antagonists [hPTH-(3-34) and [Tyr34]hPTH-(7-34)amide] markedly inhibited PTHDA, whereas ACTH, glucagon, or big gastrin did not suppress it, suggesting an involvement of the PTH receptor in PTHDA. This PTHDA was strongly inhibited by phenylmethylsulfonylfluoride and chymostatin, but not by trypsin inhibitor, elastatinal, or inhibitors of aspartic, cysteine, or metalloproteinases, suggesting that it is due to a seryl chymotrypsin-like endopeptidase. Analysis of chymotrypsin-digested products of hPTH-(1-84) eluted from HPLC exhibited five fragments detected by UV absorbance (210 nm), three of which were measurable by PTH RIA, and each corresponded to the three PTH fragments produced by OK cells. All three fragments were predominantly suppressed in the presence of chymostatin, suggesting that chymotrypsin-like activity is solely responsible for PTHDA in intact OK cells. To further explore the cleavage sites of PTH by chymotrypsin, amino acid analysis of chymotrypsin-cleaved products was performed. The results strongly support the conclusion that a chymotrypsin-like enzyme in OK cells cleaved the hormone between residues 23-24, and 34-35 to produce, at least, hPTH-(24-84) and -(35-84). Lysosomal blockers (chloroquine, ammonium chloride, or monensin) did not affect this PTHDA. Our present study indicates that chymotrypsin-like endopeptidase, but not other endopeptidase or lysosomal enzymes, is responsible for the limited hydrolysis of PTH by intact OK cells.
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PMID:Parathyroid hormone degradation by chymotrypsin-like endopeptidase in the opossum kidney cell. 305 60

A review of neuroendocrine features in breast carcinomas is presented and markers for neuroendocrine cells are discussed. Immunostaining for neuron specific enolase is the best screening marker for neuroendocrine cells in breast carcinomas, but immunoreactivity for hormones is not present in all neuron specific enolase (NSE) positive cases. Normal myoepithelial cells are also NSE positive. Thirty per cent of breast carcinomas are NSE positive. Biochemical demonstration of ACTH, PTH and calcitonin, and immunohistochemical demonstration of ACTH, bombesin, serotonin, prolactin, gastrin, VIP, leu-enkephalin, pancreatic polypeptide, beta-endorphin and sub P has been reported in breast carcinomas. Neuroendocrine cells have not been convincingly demonstrated in the normal breast or in benign breast lesions.
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PMID:Neuroendocrine differentiation in breast lesions. 329 Aug 69

Neuroendocrine tumours of upper gastrointestinal tract fall into two main categories. First carcinoid tumours of the stomach and duodenum and secondly endocrine pancreatic tumours. The endocrine tumours of the gastric mucosa include two main types, so called ECL-oma of the corpus and fundic region and gastrin producing carcinoids or hyperplasia of the antrum and duodenum. The endocrine tumours of pancreas include entopically secreting insulinomas, glucagonomas, somatostatinomas, PP-omas, and ectopically secreting tumours, such as gastrinomas and tumours producing ACTH, GHRH, and calcitonin. The diagnosis of a neuroendocrine tumour of the upper gastrointestinal tract is based on the recognition of certain clinical syndromes and the determination of certain humoral products. A broad battery of radioimmunological assays for determination of different peptides is mandatory for the diagnosis and follow up of these patients. The diagnosis is also based on histological and immunocytochemical investigation of tissue specimens obtained at operation or by biopsy. Ultrasound investigation is the best non-invasive technique to detect metastases from neuroendocrine gut and pancreatic tumours, but angiography might unveil metastases down to a size of less than 5 mm. Surgery is still the primary treatment procedure but other treatments are needed because many patients have metastases already at the time of diagnosis. Chemotherapy with streptozocin combined with 5-fluorouracil or adriamycin and human leucocyte interferon has demonstrated objective response rate of about 70%. The new somatostatin analogue SMS 201-995 is an important adjunct in controlling clinical symptoms in patients with neuroendocrine gut and pancreatic tumours. A combination of different treatment procedures is needed for long-term management of these patients.
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PMID:Neuroendocrine tumours of the upper gastrointestinal tract and pancreas. 329 22

Recent data on the immunolocalization of regulatory peptides and related propeptide sequences in endocrine cells and tumors of the gastrointestinal tract, pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptides are the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, alpha-MSH and CLIP (corticotropin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenaline-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.
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PMID:Endocrine cells producing regulatory peptides. 329 70

A tabular synopsis is presented for articles concerned with the effects of peptides on the central nervous system that appeared in the journal Peptides from 1980-1985. A table arranged alphabetically by peptide and one arranged by effects, both listing routes of injection, species, direction of change, and qualifying notes, provides easy cross-referencing of peptides and their effects. Over 80 peptides and over 135 effects are listed. The list of peptides includes, but is not limited to: ACTH, angiotensin, bombesin, bradykinin, calcitonin, casomorphin, CCK, ceruletide, CGRP, CRF, dermorphin, DSIP, dynorphin, endorphins, enkephalins, GRF, gastrin, LHRH, litorin, metkephamid, MIF-l, motilin, MSH, NPY, NT, oxytocin, ranatensin, sauvagine, substances P and K, somatostatin, TRH, VIP, vasopressin, and vasotocin. The list of effects includes, but is not limited to: aggression, alcohol, analgesia, attention, avoidance, behavior, cardiovascular regulation, catalepsy, conditioned behavior, convulsions, dopamine binding and metabolism, discrimination, drinking, EEG, exploration, feeding, fever, gastric secretion, GI motility, grooming, learning, locomotor behavior, mating, memory, neuronal activity, open field, operant behavior, rearing, respiration, satiety, scratching, seizure, sleep, stereotypy, temperature, thermoregulation and tolerance.
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PMID:Central nervous system effects of peptides, 1980-1985: a cross-listing of peptides and their central actions from the first six years of the journal Peptides. 353 8

Twelve of 87 pituitary adenomas from patients with acromegaly, Cushing's syndrome. Nelson's syndrome, hyperprolactinaemia and without symptoms of hormone hypersecretion contained gastrin in concentrations from 0.5 to 166 pmol/g. Only ACTH-producing tumours contained gastrin, which occurred in forms smaller than those present in the normal adenohypophysis. The results indicate that corticotropic tumours may synthesize gastrin in moderate amounts.
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PMID:Gastrin in pituitary tumours. 361 87

Five carcinoid tumors of the thymus were screened immunohistochemically for the occurrence of neuropeptides (ACTH, calcitonin, calcitonin gene-related peptide, cholecystokinin, gastrin, neurotensin, somatostatin, substance P), as well as of serotonin, chromogranin A, and neuron-specific enolase. Most of the patients exhibited local symptoms evoked by growing tumor masses in the upper mediastinum without any clinical evidence of endocrine activity. Light and electron microscopic examination showed characteristic uniform large epithelial cells in polar or palisade arrangement, containing variable amounts of electron-dense secretory granules. Only a few of the tested neuropeptide antisera reacted with the investigated tumors. Cholecystokinin-immunoreactive cell populations were seen in all tumors. Expression of neurotensin could be observed in three neoplasms, two of which also exhibited ACTH immunoreactivity. Chromogranin A-immunoreactive cells were found in two neoplasms. Neuron-specific enolase showed strong staining in three tumors, one of the tumors also being immunoreactive for calcitonin. The results were confirmed by control reactions. Apart from the demonstration that conventional marker proteins are not reliable in identifying all carcinoid tumors, the present study proves that the visualization of neuropeptide-immunoreactive cells in thymus carcinoids does not necessarily correspond to the manifestation of the clinical symptoms. Furthermore, each of the investigated neoplasms, as also known from other carcinoid tumors, appears to be able to produce more than one hormone.
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PMID:Carcinoid tumors of the thymus. An immunohistochemical study. 366 30

A morphologic, histochemical, and immunocytochemical study of 20 cases of pure gastrointestinal carcinoids, adenocarcinomas, and mixed neoplasms composed of both elements, so-called composite carcinoma-carcinoid tumors (CCC), was undertaken in order to correlate the morphologic patterns with the immunocytochemical localization of carcinoembryonic antigen (CEA), serotonin, and a battery of polypeptide hormones (calcitonin, glucagon, insulin, gastrin, somatostatin, and adrenocorticotropin [ACTH]). Paraffin sections from five pure carcinoids, seven pure adenocarcinomas, and eight CCC from the stomach, small bowel, appendix, and colon were studied with mucicarmine, silver impregnation stains, and a peroxidase-anti-peroxidase technic. Of the eight CCC, all were mucin positive, four were argyrophilic, and three were argentaffin positive. CEA was present in all eight, serotonin in seven, and calcitonin in one. No other neurohormonal peptides were demonstrated. The distribution of serotonin and CEA generally corresponded to the morphologic pattern, but discordance was observed in two cases, i.e., serotonin was not always localized to areas of carcinoid and CEA not always confined to areas of carcinoma. All five pure carcinoids demonstrated intracytoplasmic localization of serotonin, whereas none contained intracytoplasmic CEA. In two cases, CEA was present within acinar lumens only. The seven colonic adenocarcinomas were argyrophil and argentaffin negative. All contained CEA within the cytoplasm and in gland lumens. None contained serotonin. None of the neurohormonal peptides was localized in either pure adenocarcinomas or carcinoids. This study reveals that among gastrointestinal neoplasms displaying morphologic patterns of adenocarcinoma and carcinoid, immunocytochemical localization of CEA and serotonin confirms their bidirectional differentiation and justifies the designation "composite carcinoma-carcinoid."
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PMID:Composite carcinoma-carcinoid tumors of the gastrointestinal tract. A morphologic, histochemical, and immunocytochemical study. 389 86

Twenty-seven cases of medullary carcinoma of the thyroid gland (MCT) were studied by light microscopy, immunocytochemistry, and electron microscopy. Immunoreactivity for neuron-specific enolase (NSE) and calcitonin was present in all tumors. The numbers of peptides and serotonin demonstrated in each case varied from one to eight. Bombesin was present in 18 of the 27 cases, serotonin in 15, leu-enkephalin in 8, somatostatin in 8, gastrin in 3, substance P in 1, vasoactive intestinal peptide (VIP) in 1, and ACTH in 1. Insulin and glucagon were not encountered in any of the tumors. Immunoreactivity for thyroglobulin was seen in five primary tumors as well as in one lymph node metastasis. The finding of concurrent production of calcitonin and thyroglobulin within the same tumor is enough to question the dogma of the separate origin of follicular cells and C-cells. We were unable to attach any clinical importance to the production of multiple peptides and/or amines.
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PMID:Medullary carcinoma of the thyroid gland: an immunocytochemical study. 390 54

The antitumor action of the 2-chloroethylnitrosocarbamoyl derivatives of peptides related to the 9-13 amino acid residues of alpha-MSH/ACTH and of the C-terminal tetrapeptide analogue of gastrin have been investigated. Series of 2-chloroethylnitrosoureas attached to amino acids, di-, tri-, tetra-, or pentapeptides were examined in a primary screening system. Among these compounds the Pro-Val-, Lys-Pro-Val-, and Trp-Gly-Lys-Pro-Val-containing 2-chloroethylnitrosocarbamoyl groups were the most effective in the L1210 system. The human melanoma xenograft line was also affected by these agents, while colorectal xenografts were insensitive. A combination of tripeptide-2-chloroethyl-nitrosourea with BCNU induced more than additive growth inhibition of L1210 leukemia.
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PMID:Antitumor action of N-(2-chloroethyl)-N-nitrosocarbamoyl derivatives of biologically active polypeptide hormone fragments. 394 98


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