Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endocrine tumours (argyrophil cell carcinoids) are frequent in the oxyntic mucosa of mastomys. The tumour is notable for its high histamine content and for its high histidine decarboxylase activity. The tumour is thought to arise from the histamine-storing, enterochromaffin-like cells of the oxyntic mucosa. They are of two ultrastructurally distinguishable types, ECL cells and A-like cells, both of which have been demonstrated in the tumour. Identical cells have been demonstrated in the oxyntic mucosa of the rat; there is much evidence that in this species the functional activity and the number of these cells are determined by the serum gastrin concentration. However, tumours have never been found to arise from these cells in the rat. As an initial step in an attempt to explain the formation of the gastric endocrine tumour in the mastomys we examined the distribution and frequency of occurrence of endocrine cells in the mastomys stomach. Gastrin cells in the antrum of mastomys seemed to occur in about the same frequency as in the antrum of rat and mouse. 5-HT-storing enterochromaffin cells, however, were considerably more numerous in the mastomys, whereas the somatostatin cells in the antrum were fewer. The number of enterochromaffin-like cells and somatostratin cells in the oxyntic mucosa of mastomys was much lower than in the rat and mouse. Once developed, the gastric endocrine tumour seems to reduce the antral gastrin cell number; the larger the tumour the greater the reduction.
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PMID:Spontaneous argyrophil cell carcinoid in the glandular stomach: immunohistochemical study of gastric endocrine cells in normal and tumour-bearing mastomys. 38 3

At present at least seven different endocrine cell types have been identified in the stomach. According to their relative frequency and secretion products the antral gastrin producing G cell and somatostatin producing D cell and the fundic histamine producing ECL cell are the best characterized cell types. Total endocrine cell mass is controlled by various factors from inside and outside the stomach. Density of antral G and D cells depends on the presence and absence of food, on the antral pH and on additional humoral and/or neural factors. Gastrin and not gastric pH has been identified as the most important factor regulating the density of fundic ECL cells. Adaptation of gastric endocrine cells to gastric pH and to the presence, abundance or absence of humoral and neural regulators are well known phenomena though only partially understood. Antral G cells increase and antral D cells decrease during long-term achlorhydria which as a consequence leads to hypergastrinaemia. Examples are pernicious anaemia in man and drug-induced acid suppression under experimental conditions. Interestingly, achlorhydria-induced G cell hyperplasia never progresses to gastrinomas. Fundic ECL cell density increases markedly in the presence of long-lasting hypergastrinaemia independently of gastric pH. In contrast to G cells ECL cell hyperplasia may progress to rarely occurring ECLomas. However, this depends on additional conditioning factors as the presence of severe atrophic gastritis as in pernicious anaemia or a specific genetic trait present in patients with gastrinomas associated with the MEN I syndrome.
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PMID:Adaptation and renewal of the endocrine stomach. 129 54

Gastric acid secretion is regulated by an intricate interplay of neural (acetylcholine), hormonal (gastrin), and paracrine (histamine, somatostatin) mechanisms. Receptors for each of these agents and the signal transduction pathways to which these receptors are coupled have been identified on the parietal cell. The stimulatory effect of acetylcholine and gastrin is mediated by an increase in cytosolic calcium, whereas that of histamine is mediated by activation of adenylate cyclase and generation of cAMP. Strong potentiation between histamine and either gastrin or acetylcholine reflects postreceptor interaction between the distinct pathways as well as the ability of acetylcholine and gastrin to release histamine from mucosal ECL cells. The inhibitory effects of somatostatin on acid secretion are mediated by receptors coupled by guanine nucleotide-binding proteins to inhibition of adenylate cyclase activity. All the pathways converge on and modulate the activity of the luminal enzyme, H+K(+)-ATPase, the proton pump of the parietal cell. Precise information on the mechanisms involved in gastric acid secretion has led to the development of potent drugs capable of inhibiting acid secretion. These include competitive antagonists that interact with stimulatory receptors (e.g., histamine H2-receptor antagonists) as well as noncompetitive inhibitors of H+K(+)-ATPase (e.g., omeprazole). The histamine H2-receptor antagonists (cimetidine, ranitidine, famotidine, and nizatidine) continue as first-line therapy for peptic ulcer disease and are effective in preventing relapse. Although they are generally well tolerated, histamine H2-receptor antagonists may cause untoward CNS, cardiac, and endocrine effects as well as interference with the absorption, metabolism, and elimination of various drugs. Omeprazole is a weak base that reaches the parietal cell through the bloodstream, diffuses through the cytoplasm, and becomes activated and trapped as a sulfenamide in the acidic canaliculus of the parietal cell. It covalently binds to H+K(+)-ATPase, thereby irreversibly blocking acid secretion in response to all modes of stimulation. The main drawback to its use is its extreme potency, which leads to virtual anacidity, gastrin and ECL cell hyperplasia, hypergastrinemia, and, in rats, to the development of carcinoid tumors.
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PMID:Control of gastric acid secretion. Histamine H2-receptor antagonists and H+K(+)-ATPase inhibitors. 135 65

Receptors for the main neural (acetylcholine), hormonal (gastrin) and paracrine (histamine) secretory stimulants and the signal transduction pathways to which these receptors are coupled have been identified on the parietal cell. The stimulatory effect of histamine is mediated via an increase in adenylate cyclase activity, whereas the effect of acetylcholine and gastrin are mediated via an increase in cytosolic levels of calcium. Strong synergism between histamine and either gastrin or acetylcholine may reflect postreceptor interaction between the distinct pathways. Acetylcholine and gastrin are also capable of releasing histamine from the gastric mucosa, probably from ECL cells. The inhibitory effects of somatostatin and prostaglandin E on acid secretion are mediated by receptors coupled via guanine nucleotide binding proteins to inhibition of adenylate cyclase activity. All the pathways converge on and modulate the activity of the luminal enzyme, H+K(+)-ATPase, ultimately responsible for acid secretion. The intramural neural and paracrine pathways involved in the regulation of gastrin secretion in the antrum and acid secretion in the fundus have also been identified. Of prime importance is the somatostatin cell, which exerts a paracrine restraint on gastrin secretion and acid secretion. Elimination of this restraint or disinhibition is one of the mechanisms by which the stimulatory influence of cholinergic neurons is exerted on gastrin and parietal cells. Gastrin secretion is regulated by a cholinergic neuron that causes inhibition of somatostatin secretion and thus stimulation of gastrin secretion (disinhibition) and a noncholinergic neuron that causes direct stimulation of gastrin secretion by releasing the neurotransmitter, bombesin (or gastrin-releasing peptide). Acid secretion is regulated by a cholinergic neuron that causes direct stimulation of the parietal cell and indirect stimulation by decreasing somatostatin secretion, thus eliminating its inhibitory effect on the parietal cell (disinhibition). In addition, a regulatory feedback mechanism exists whereby intraluminal acidification stimulates somatostatin secretion, which in turn attenuates acid secretion. Gastric acid secretion may also be regulated by one or more intestinal inhibitory hormones, the most likely candidates being secretin, intestinal somatostatin, and neurotensin. Enterogastrone activity probably reflects the combined effect of all these hormones. Precise information on receptors and signal transduction mechanisms as well as on intramural neural and paracrine regulatory pathways has led to the development of new drugs capable of inhibiting acid secretion. These include antagonists that interact with stimulatory receptors (histamine H2-receptor antagonists, muscarinic receptor antagonists, and gastrin receptor antagonists), agonists that interact with inhibitory receptors (somatostatin and prostaglandin E analogues), and irreversible inhibitors of the luminal enzyme, H+K(+)-ATPase.
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PMID:Control of acid secretion. 169 38

The oxyntic mucosa of the human stomach harbors at least five different endocrine cell types (ECL cells, A-like or X cells, somatostatin cells (D), enterochromaffin (EC) cells, and D1 or P cells). Little is known about their functional roles, and of the hormones they produce only somatostatin has been identified. The relative frequency and regional distribution of the different endocrine cell populations were studied in 13 adults with no manifest gastrointestinal disease. From each of them at least three biopsy specimens were taken at seven fixed locations within the oxyntic mucosa. The specimens were examined for the different endocrine cell types by means of immunocytochemistry (staining with antisera against chromogranin A,5-hydroxytryptamine, and somatostatin) and silver staining techniques (demonstration of argyrophil cells by the methods of Grimelius or Sevier-Munger). Chromogranin-positive cells included all endocrine cells identified by the other staining techniques. Grimelius-positive cells included all endocrine cells except the somatostatin cells. Sevier-Munger-positive cells, finally, included the ECL cells and the EC cells. The frequency of ECL cells could be calculated by subtracting the number of EC cells from the number of Sevier-Munger-positive cells. The ECL cells represented 35% of the total endocrine number, somatostatin cells 26%, and EC cells 25%. The remaining 14% consisted of A-like cells, D1 cells, and P cells. Generally, the endocrine cells predominated in the basal portion of the glands, but the various populations of endocrine cells were not uniformly distributed in the various regions of the oxyntic mucosa. However, representative specimens could be obtained from the main body of the stomach, and the results indicate that the examination of a fairly small number of specimens from the main body of the stomach may be sufficient for assessing the frequency of endocrine cells in the oxyntic mucosa of individual patients.
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PMID:Endocrine cells in the human oxyntic mucosa. A histochemical study. 247 Jan 31

Up to 16 types of endocrine cells have been characterized morphologically (and most of them also functionally) in the gastroenteropancreatic area. Four main groups of pancreatic endocrine tumors (with several subtypes) have been identified: islet cell, ectopic, nonfunctioning, and poorly differentiated tumors. A detailed classification system that combines cytologic and clinicopathologic patterns has been developed for the study of 132 pancreatic tumors. Among a large series (more than 120 cases) of endocrine tumors arising in the gastrointestinal tract, serotonin-producing argentaffin carcinoids have been separated from hindgut trabecular carcinoids, producing glucagon- and pancreatic polypeptide-related peptides, paragangliomas, somatostatin cell tumors, gastrinomas, and argyrophil ECL cell carcinoids. The clinicopathologic profile of the various pancreatic and gastrointestinal tumor entities has been delineated and involvement in the multiple endocrine neoplasia syndrome has been analyzed in detail.
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PMID:The gastroenteropancreatic endocrine system and related tumors. 257 1

Gastrin-immunoreactive cells were fairly numerous in the pancreas and upper duodenum of the rat at about the time of birth. A minor population of these cells stained with antibodies directed against the N-terminal region of gastrin-34 as well as with antibodies directed against the C-terminal region. The remainder of the cells stained with the C-terminally directed antibodies only. Within a fortnight after birth all gastrin-immunoreactive cells disappeared from the pancreas and were greatly reduced in number in the duodenum; those that remained were probably CCK cells. Gastrin cells were rare in the antrum at birth and remained rare during the first days after birth. They increased in number, slowly until after weaning (15-20 days of age) and then more rapidly, until 25-30 days of age when the gastrin cell density reached that in adult rats. At the time of birth the gastrin concentration in serum was low; the subsequent increase during the first 2 weeks paralleled the development of the antral gastrin cell system. Adult postprandial serum gastrin concentrations were reached 12 days after birth. Somatostatin cells were rare in both the antral and oxyntic mucosa at birth. They increased gradually in number until about a month after birth when the cell density reached that seen in adult rats. In the oxyntic mucosa the ECL and A-like cells are the predominant endocrine (argyrophil) cell types. They were not detected until about 4 days after birth. Their number increased slowly until about 30 days of age. They did not stain argyrophil until about 2-4 weeks after birth. Parietal cells were few at birth; ultrastructurally they appeared to be in an active state and histochemically they were shown to contain carbonic anhydrase. The pH of the gastric content of newborn rats was close to 5; 15-17 days after birth the pH was about 4 in freely fed rats. In fasted rats shortly after birth the pH was about 4. Two weeks later it was around 2, which is the pH measured in older rats. Hence, the full capacity for acid secretion is probably not established until weaning. Fasting greatly lowers the serum gastrin concentration and the histidine decarboxylase activity of the ECL cells in adult rats. Before weaning, fasting produced these effects only to a minor degree.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endocrine cells and parietal cells in the stomach of the developing rat. 286 80

Chromogranins A and B and secretogranin II have been localized in a wide spectrum of gastroenteropancreatic endocrine/paracrine cells. Chromogranin A immunoreactivity showed the widest distribution and was displayed by glucagon-, PP-, gastrin-, gastrin-CCK-, secretin-immunoreactive cells, the most intense stainings being peculiar of enterochromaffin cells. Chromogranin B immunoreactivity was detected in gastrin- and glucagon cells and in some enterochromaffin cells containing also chromogranin A. Secretogranin II was paired to chromogranin A in glucagon cells of pancreatic islets or occurred alone in glycentin/PP cells of colonic mucosa. Neither of the chromogranins nor secretogranin II have been so far detected in somatostatin-, GIP-, or motilin-immunoreactive cells. Chromogranin A but not chromogranin B or secretogranin II has been detected in the gastric argyrophilic ECL cells.
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PMID:Chromogranins A and B and secretogranin II in hormonally identified endocrine cells of the gut and the pancreas. 322 65

Neoplastic proliferations of neuroendocrine cells (NE) may occur throughout the entire GI tract but affect particularly appendix and ileum ("midgut carcinoids"), rectum ("hindgut carcinoids"), as well as stomach and the duodenum ("foregut carcinoids"). Only more exceptionally, they arise in the esophagus, jejunum and colon. The NE tumors encompass a heterogeneous gross and microscopic structural spectrum, ranging from inconspicuous microproliferations ("mucous membrane nevi") to bulky tumor masses. Their growth patterns are usually characteristic and easily recognized. In doubtful cases their NE differentiation becomes established by a characteristic silver affinity, by the ultrastructurally observed presence of characteristic "endocrine" secretion granules, and by immunohistochemically detectable occurrence of "pan-NE markers" (neuron-specific enolase, chromogranins, and synaptophysin), biogenic amines (mainly serotonin), and neurohormonal peptides. Foregut carcinoids usually contain serotonin, gastrin, and somatostatin, midgut carcinoids often only serotonin and tachykinins, whereas the hindgut carcinoids as a rule are multihormonal with a wide spectrum of hormonal peptides, including even insulin. Most GI NE tumors are found in the appendix (50%) and the ileum (30%). Practically all (98%) of the appendiceal NE tumors are benign. They have recently been proposed as arising from apparently Schwann-cell-related NE cells in the submucosa, whereas the ileal--and probably also all the other non-appendiceal NE tumors--are derived from the totipotential cells in epithelial crypts of the mucosa. Among the ileal NE neoplasms a large number can metastasize and result in a fatal outcome. The ability to metastasize is related to the size and to the multiplicity of the primary tumors at the time of initial diagnosis and, to some extent, to their histopathologic growth pattern. Now, some relationship between the prognosis and the cytochemically assessed nuclear DNA content of the NE tumor cells has also been established; not less than about 1/4 to 1/3 seem to be aneuploid. Almost 90% of the rectal carcinoids are benign. Exceptionally, a highly malignant NE neoplasms can arise from the colon/rectum--as well as from the esophagus--composed of NE cells of small and intermediate size. The NE tumors of the stomach are often composed of ECL (enterochromaffin-cell-like) cells; such ECL cell carcinoids are related to atrophic gastritis with pernicious anemia; experimentally, they can be induced by hypergastrinemia in rats. Duodenal carcinoids often contain psammoma bodies and can be associated with neurofibromatosis.
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PMID:Neuroendocrine tumors of the gastrointestinal tract. 329 Aug 66

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


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