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

Gastrinomas from 25 patients were examined by immunohistochemistry (IHC) and in situ hybridization histochemistry (ISH). Most patients (84%) presented with the Zollinger-Ellison syndrome. Six had multiple endocrine neoplasia type I (MEN-I). Twelve patients (48%) had duodenal primaries and 11 of 12 of these had metastases to regional lymph nodes and/or liver in spite of the small sizes of the primary tumors (mean size of 0.9 cm). Five patients had pancreatic gastrinomas and eight patients had metastatic tumor in regional lymph nodes or liver at surgery but a primary was not found. IHC and ISH analyses showed that all cases were positive for gastrin protein and 24 of 25 (96%) expressed gastrin mRNA that was easily detected in formalin-fixed, paraffin-embedded tissue sections. Both benign and malignant tumors expressed alpha subunit of human chorionic gonadotropin protein (alpha-HCG). However, only malignant gastrinomas (29%) expressed adrenocorticotropic hormone protein or proopiomelanocortin (POMC) mRNA. ISH and Northern hybridization analysis revealed that chromogranin A mRNA was the most common member of the chromogranin/secretogranin (Cg/Sg) family which was expressed in both benign and malignant gastrinomas. These results indicate that duodenal gastrinomas are common in both sporadic and MEN-1-associated cases, and small duodenal primaries may be associated with extensive regional lymph node and liver metastases. Expression of ACTH/POMC protein and mRNA was consistently associated only with malignant gastrinomas while gastrin protein, gastrin mRNA and Cgs/Sgs mRNAs were readily detected in both benign and malignant gastrinomas.
 ...
PMID:Analysis of gastrinomas by immunohistochemistry and in situ hybridization histochemistry. 128 76

Chromogranins (Cg) and secretogranins (Sg) are acidic proteins localized in the secretory granules of a large variety of endocrine cells collectively named APUD cells (amine precursor uptake and decarboxylation). To examine the possible function of Cg/Sg as amine storage proteins, enteroendocrine cells of the rat gastric antral mucosa, i.e., serotonin-containing enterochromaffin (EC)-cells, gastrin (G)-, and somatostatin (D)-cells, were investigated immunohistochemically in serial semi-thin sections of controls and after intervention in serotonin synthesis. CgA and CgB immunoreactivity was determined semiquantitatively by optical density measurements. Experiments included inhibition of serotonin synthesis by p-chlorophenylalanine (pCPA), exogenous application of the serotonin precursor 5-hydroxytryptophan (5-HTP), and a combination of both treatments. The cellular distribution of Cg and the density of its immunoreactivity were closely related to the primary content of serotonin and the ability to store serotonin after 5-HTP application. Thus, Cg may act as amine-binding proteins in enteroendocrine cells, binding most probably being due to ionic interactions between Cg and the biogenic amines. EC- and G-cells, however, differed in their amine-handling properties and in the response of their Cg immunoreactivity after intervention in serotonin synthesis. We conclude, therefore, that the physiological function of Cg as amine storage proteins is restricted to endocrine cells with an endogenous content of amines. In other endocrine cells, exhibiting only a potential amine production, APUD may be considered as a kind of supravital staining without physiological significance.
 ...
PMID:Serotonin storage and chromogranins: an experimental study in rat gastric endocrine cells. 135 16

The chromogranins A and B (CgA and CgB, respectively), originally detected in the adrenal medulla, are present in various endocrine organs. Remarkably, their immunoreactivities vary among different endocrine cell types and also within a given endocrine cell population. With densitometric techniques at the cellular level, individual gastrin cells (n = 318) from guinea pig antral mucosa were studied to measure their content of immunoreactive CgA, CgB, and gastrin. The composition of these secretory proteins in individual gastrin cells varied considerably but with predictable components. Statistical evaluation of the data showed that immunoreactivities for gastrin and CgA correlated negatively in these cells; CgA and CgB immunoreactivities also correlated inversely. On the other hand, immunoreactivities for gastrin and CgB exhibited a high positive correlation. The mutual relationships between gastrin, CgA, and CgB suggest that under physiological conditions biosynthetic pathways of these secretory constituents are linked to each other in individual gastrin cells.
 ...
PMID:Mutual relationships between chromogranins A and B and gastrin in individual gastrin cells. 155 98

Pancreastatin is a 49 amino acid comprising peptide isolated from porcine pancreas that is derived by proteolytic processing from chromogranin A. Using an antibody against the synthetic C-terminal fragment pancreastatin (33-49), we examined the light and electron microscopical immunocytochemical localization of this peptide in porcine tissues. Pancreastatin-like immunoreactivity (PLI) was found in pancreatic somatostatin-, insulin- and glucagon cells in varying intensities; pancreatic polypeptide cells were always negative. At the electron microscopical (EM) level the immunoreactivity was confined to the electron dense core of the secretory granules in the case of somatostatin and insulin cells or to the less electron dense "halo" of the glucagon granules. In the antrum PLI positive cells represented gastrin (G), somatostatin (D) and enterochromaffin (EC) cells, in the duodenum in addition to EC- and G-cells a small number of PLI positive cells showed a positive immunoreaction for glucagon-like peptide (GLP) I and secretin in serial sections. Both norepinephrine and epinephrine containing cells of the adrenal medulla exhibited a strong reaction for PLI. In the pituitary several cell populations stained with varying intensities, including gonadotrophs and thyrotrophys. PLI is present in a distinct and characteristic subpopulation of neuroendocrine cells in various organs. The subcellular localization may indicate a function in the granular concentration, packaging and storage of peptides and amines in the brain-gut endocrine system.
 ...
PMID:Light and electron microscopical immunocytochemical localization of pancreastatin-like immunoreactivity in porcine tissues. 218 73

Pancreastatin, a new 49-amino acid peptide, has recently been isolated and characterized from extracts of the porcine pancreas. The objective of the present study was to examine the effect of various doses of pancreastatin on gastric acid secretion in conscious dogs that were prepared with chronic gastric cannulas. Pancreastatin, administered IV at 400 pmol.kg-1 x h-1, enhanced peptone meal [peptone (5%), phenylalanine (90 mmol/L), glucose (12 g/dL)]-stimulated gastric acid secretion by 50%; pancreastatin at 800 pmol.kg-1 x h-1 enhanced peptone meal secretion by 165% (P less than 0.05). Intravenous administration of pancreastatin did not affect basal or peptone-stimulated release of gastrin. In addition, IV pancreastatin (400 pmol.kg-1 x h-1) failed to influence basal gastric acid secretion. Pancreastatin did not affect acid secretion stimulated by 2-deoxyglucose, histamine, or pentagastrin. The present study shows that pancreastatin can selectively enhance gastric acid secretion by a mechanism independent of cholinergic, histaminergic, or gastrin input.
 ...
PMID:Stimulatory effect of pancreastatin on gastric acid secretion in conscious dogs. 234 41

To clarify the relationship between the neuroendocrine expression of prostatic carcinoma and prognosis, we studied immunohistochemically formalin-fixed and paraffin-embedded tissue sections from 30 cases of prostate cancer by means of neuroendocrine (NE) differentiation markers. The rate of NE positive-staining cases was 40% (12/30), and more than two kinds of NE markers were expressed in 9/12 cases. The NE markers were NSE (7 positive cases), Chromogranin-A (7), Calcitonin (2), Gastrin (2), hCG (4), S-100 Protein (2), Serotonin (3), EMA (23) and Lillie argentaffin staining (2). Follow-up of the 30 patients showed that NE negative tumors have a prognosis better than NE positive tumors (P < 0.005). Their poor prognosis is due to poor response to endocrine therapy, and the mechanism is that some neuropeptides secreted by NE cells affect the growth of tumor cells. Finally, how to improve the prognosis of the patients who have NE expression of their prostate cancer is discussed.
 ...
PMID:[Relation between neuroendocrine expression of prostatic carcinoma and prognosis]. 803 80

The effects of long term (6-month), high (500-micrograms), once a day administration of octreotide on enterochromaffin-like (ECL) cell proliferation were evaluated in eight patients with hypergastrinemic atrophic gastritis at risk for the development of gastric carcinoids. Fasting gastrin levels were determined during treatment and up to 6 months after the end of treatment. Chromogranin A, hCG alpha, and somatostatin-immunostained cells were morphometrically evaluated in biopsy specimens of corpus mucosa taken before and after treatment. The results showed that gastrin levels significantly decreased from 950 to 238 ng/L (-74.9%; P < 0.01) at the end of treatment, a decrease that persisted 6 months after the end of treatment (450 ng/L; P < 0.05). The volume density of CgA cells (mostly ECL cells) decreased from 3.7% to 2.1% of the epithelial component (-43%; P < 0.014), that of hCG alpha-storing ECL cells decreased by 85% (P < 0.0007), and that of somatostatin-stained cells decreased by 74% (P < 0.04). No clinically significant side-effects were found. It is concluded that octreotide treatment as used in the present study is safe and effective in reducing hypergastrinemia and associated ECL cell changes in patients with atrophic gastritis. The decrease in D cells is consistent with the occurrence of somatostatin receptors and related autocrine regulation in these cells.
 ...
PMID:Effectiveness of octreotide in controlling fasting hypergastrinemia and related enterochromaffin-like cell growth. 863 88

1. Vesicular monoamine transporters (VMATs) translocate monoamines from the cytoplasm into secretory vesicles of endocrine cells and neurones, but they have limited affinity for histamine, and the identity of the vesicular transporter for this monoamine is uncertain. The aims of the present study were to characterize VMAT representatives in rat gastric corpus, and to determine if their expression was regulated by factors that modulate histamine biosynthesis. 2. Polymerase chain reaction (PCR) cloning using oligonucleotide primers to DNA sequences conserved within the VMAT family provided evidence for VMAT2, but not VMAT1 in rat gastric corpus. Northern analysis using a VMAT2 complementary RNA probe revealed a single 4 kb mRNA species in corpus endocrine cells. 3. In rats treated for up to 5 days with the H(+)-K(+)-ATPase inhibitor omeprazole, VMAT2, histidine decarboxylase and chromogranin A mRNA abundance in gastric corpus, and plasma gastrin concentrations increased progressively. Omeprazole also elevated VMAT2 expression in rats fasted for 48 h, but fasting alone, or refeeding fasted animals had no effect. 4. The results are consistent with a role for VMAT2 in the transport of histamine into enterochromaffin-like cell secretory vesicles, and with upregulation of the transporter to accommodate the increased histamine biosynthesis and secretion that accompanies achlorhydria.
 ...
PMID:Expression and regulation of a vesicular monoamine transporter in rat stomach: a putative histamine transporter. 874 92

Due to the increased costs of medical care, a cost-benefit analysis is needed when trying for the 'ultimate' biochemical diagnosis of gastro-enteropancreatic (GEP) tumours. The glycoprotein chromogranin family has proved useful in screening for neuroendocrine tumours. In patients with midgut carcinoid tumours, chromogranin A is more sensitive than urinary 5-hydroxyindoleacetic acid but by combining these two biochemical markers most GEP tumours can be diagnosed. Chromogranin A is also a prognostic marker for survival in patients with midgut carcinoid tumours. Pancreastatin constitutes a part of the chromogranin A molecule and is a less sensitive general screening marker for neuroendocrine gut and pancreatic tumours, but levels, in combination with chromogranin A, might give some insight into tumour biology. Specific markers such as gastrin, glucagon, vasoactive intestinal peptide, insulin, neuropeptide K and substance P should be used to further characterise hormone production in neuroendocrine tumours. However, in some patients, confirmation of diagnosis requires provocation tests, such as the secretin or meal provocation tests. Staging information can be obtained by new investigations such as intra-operative or endoscopic ultrasound, octreoscan, and positron emission tomography. We combine the biochemical characterisation of neuroendocrine tumours with studies of growth factors/receptors, adhesion molecules, proliferation markers, somatostatin receptor content, induction of the enzymes p68 kinase and 2'5'-A-synthetase, and apoptosis, to establish a sound rationale for therapeutic decisions, enabling every patient to receive individualised treatment.
 ...
PMID:The ultimate biochemical diagnosis of gastro-enteropancreatic tumours. 881 68

The ontogeny of endocrine cells and nerve fibers containing immunoreactivities for 12 regulatory peptides and serotonin was studied in the digestive tract of a flatfish, the turbot (Scophthalmus maximus), using antisera specific for mammalian and teleostean hormones. Transient insulin-immunoreactive (-IR) endocrine cells were detected from day 5 to day 10 in stomach and intestine I. Somatostatin (SOM)-IR cells appeared at day 8 in the stomach anlage and intestine I. In contrast to the islet cells, they reacted with antisera against mammalian (m) SOM-14 and salmon (s) SOM-25. Infrequent nerve fibers reacting only with anti-mSOM-14 appeared around day 24. Thus, different forms of SOM seem to be present in the gastro-entero-pancreatic system and the enteric nervous system. Neuropeptide Y (NPY)-, salmon pancreatic polypeptide (sPP)- and mPP-immunoreactivities coexisted throughout development. In entero-endocrine cells, NPY/PP-immunoreactivity was first observed at day 8 and around day 24 in enteric nerve fibers. Glucagon (GLUC)-IR entero-endocrine cells appeared at day 5. No coexistence of NPY/PP- and GLUC-immunoreactivities was observed. The first insulin-like growth factor I (IGF-I)-IR cells were identified around day 8. They seemed to contain none of the other peptides. Their number and distribution exhibited great interindividual differences. Vasoactive intestinal polypeptide (VIP)-IR entero-endocrine cells appeared as late as around day 24. The first VIP-IR nerve fibers, however, were identified at day 5. Infrequent neurotensin (NT)-IR cells appeared along the intestine around day 10 and NT-IR nerve fibers at day 17. The first serotonin (SER)-IR cells were observed in the stomach anlage around day 10 and SER-IR nerve fibers at day 15 throughout the gastro-intestinal tract. Gastrin (GAS)/cholecystokinin (CCK)-IR cells appeared around day 11 in stomach and intestine I. The first substance P (SP)-IR enteric nerve fibers were detected around day 8 and SP-IR endocrine cells at day 11. Pancreastatin (PST)-IR cells were identified in the stomach anlage and intestine I around day 8 and contained NT-, GAS/CCK- and SER-immunoreactivities in coexistence. Thus, several developmental phases can be distinguished: (1) at the onset of exogenous feeding only transient INS-IR cells and VIP-IR nerve fibers are present; (2) a differentiated entero-endocrine system establishes during the early phase of exogenous feeding; (3) before the final differentiation of stomach and gut GAS/CCK-IR cell appear; (4) after metamorphosis most of the different types of regulatory peptide-containing nerve fibers develop, probably setting up the fine regulation of gastro-intestinal blood flow and motility.
 ...
PMID:An immunohistochemical analysis of the ontogeny, distribution and coexistence of 12 regulatory peptides and serotonin in endocrine cells and nerve fibers of the digestive tract of the turbot, Scophthalmus maximus (Teleostei). 900 19


1 2 Next >>