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)

The number of peptide hormones which have been localized in the gut and in neurons of the central and peripheral nervous system has increased considerably. As there is almost no information about their importance in children with gastrointestinal diseases, we developed highly sensitive radioimmunoassays and measured postprandial serum/plasma levels of gastrin, secretin, vasoactive intestinal polypeptide (VIP) and motilin in 112 healthy children (N), 28 patients with cystic fibrosis (CF) and 17 children with Crohn's disease (CD). Gastrin values were not pathologic in children with CF nor those with Crohn's disease (N = 56.2 +/- 29.6 pg/ml; CF = 57.0 +/- 34.2 pg/ml; CD = 43.6 +/- 26.6 pg/ml). A significant age dependency was established for secretin and VIP. These peptides were elevated in CF-patients. In children with Crohn's disease only Secretin was increased. Motilin was elevated in all patients: N = 78.0 (49.1-124.0) pg/ml; CF = 148.0 (70.8-309) pg/ml; CD = 153.0 (87.6-266).
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PMID:[Gastrin, secretin, VIP and motilin in children with mucoviscidosis and Crohn disease]. 370 84

Regulation of pancreatic exocrine secretion is comprised of a complex interplay between hormonal and nervous mechanisms. Stimulatory gut hormones which act via the circulation include secretin, CCK, gastrin and bombesin, while VIP operates through peptidergic nervous release. Pancreatic polypeptide and glucagon are two examples of circulating inhibitory hormones while inhibition by somatostatin is through a paracrine release mechanism. Although the effects of vagal cholinergic nerves have been previously thought to be indirect through hormone release evidence is now accumulating for a direct role. Altered hormone release has been noted in chronic pancreatic insufficiency, cystic fibrosis and coeliac disease and may contribute in an important way to the pathophysiology of these malabsorptive disorders.
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PMID:Neuro-hormonal control of pancreatic function in man and its failure. 613 50

It has been claimed that plasma cholecystokinin (CCK) concentrations are raised in patients with pancreatic insufficiency. We have measured plasma CCK concentrations in 32 patients with pancreatic insufficiency (22 alcoholic pancreatitis and 10 cystic fibrosis) and in 30 normal subjects by radioimmunoassays using antibodies with different specificities. Antibody 1703 binds to COOH-terminal forms of CCK containing at least 14 amino acid residues and does not cross-react with gastrins. Antibody T204 binds to all CCK-peptides containing the sulfated tyrosyl region and shows low cross-reactivity with sulfated gastrins but no binding to nonsulfated gastrins. Antibody 5135 binds to all COOH-terminal CCK-peptides and shows full cross-reactivity with gastrins. In patients with pancreatic insufficiency, plasma CCK concentrations (1.2 +/- 0.1 pmol/liter, antibody 1703; 2.0 +/- 0.2 pmol/liter, antibody T204; 12.5 +/- 1.4 pmol/liter, antibody 5135) were not significantly different from those in normal subjects (1.1 +/- 0.1 pmol/liter, antibody 1703; 2.2 +/- 0.3 pmol/liter, antibody T204; 10.5 +/- 0.9 pmol/liter, antibody 5135). Furthermore, plasma CCK concentrations in patients with pancreatic insufficiency due to alcoholic pancreatitis (1.2 +/- 0.1 pmol/liter, antibody 1703; 1.9 +/- 0.2 pmol/liter, antibody T204; 14.0 +/- 1.9 pmol/liter, antibody 5135) were not significantly different from those in patients with cystic fibrosis (1.2 +/- 0.2 pmol/liter, antibody 1703; 2.4 +/- 0.4 pmol/liter, antibody T204, 9.1 +/- 1.0 pmol/liter, antibody 5135). Cross-reactivity with gastrin accounted for almost all CCK-like-immunoreactivity measured with antibody 5135.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma cholecystokinin concentrations in patients with pancreatic insufficiency measured by sequence-specific radioimmunoassays. 649 29

Responses of 11 gastrointestinal regulatory peptides to a standard test meal were assessed in 10 adult patients with cystic fibrosis. The basal plasma neurotensin was significantly elevated in patients with cystic fibrosis, being 31.5 +/- 6.1 pmol/L compared with a control value of 10.3 +/- 1.5 pmol/L (p less than 0.005). Plasma neurotensin remained elevated throughout the test period. Basal plasma enteroglucagon was similarly elevated, the patients with fibrocystic disease having levels of 51.3 +/- 4.6 pmol/L compared to controls with levels of 33.2 +/- 6.7 pmol/L (p less than 0.02). There was, however, no significant difference in postprandial levels of plasma enteroglucagon. Postprandial motilin was significantly elevated in the patients with cystic fibrosis; this elevation is in contrast with previous findings in children. Release of gastric inhibitory polypeptide was impaired, while release of cholecystokinin showed no significant difference in control values, although there was a tendency for delay. There was no significant postprandial rise of pancreatic polypeptide in the patients, whose levels were grossly lower than controls. Insulin showed a delayed response. No significant differences were observed between patients and controls in levels of gastrin, pancreatic glucagon, somatostatin, or vasoactive intestinal peptide. The elevation of plasma neurotensin and enteroglucagon in the basal state may reflect an adaptive response and may be part of the improved digestive function in adults compared with children with fibrocystic disease.
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PMID:Adult cystic fibrosis: postprandial response of gut regulatory peptides. 662 32

We have investigated the effect of cystic fibrosis on alimentary hormones in 10 children by measuring the pancreatic and gut hormone rsponse to a milk drink. Plasma insulin and gastric inhibitory peptide were both significantly reduced (P < 0.05 and P < 0.005, respectively, at 15 min) in the patients with cystic fibrosis, compared with controls, even though the early glucose rise was greater in the former group (P < 0.05 at 15 min). Fasting levels of pancreatic polypeptide were significantly lower in the fibrocystic children (P < 0.01), and the normal response to milk was completely abolished in these patients (P < 0.001). Fasting plasma enteroglucagon concentrations were grossly abolished in the cystic fibrosis patients (P < 0.001) and these remained elevated throughout the test. No significant differences were seen in basal or postmilk responses of plasma glucagon, gastrin, secretin, vasoactive intestinal peptide, or motilin in cystic fibrosis. It would thus appear that the pancreatic polypeptide cell is more susceptible to the effects of the disease process than the beta or alpha cell in cystic fibrosis. Some aspects of the abnormalities in the gastrointestinal endocrine system were similar to those seen in celiac disease and tropical sprue and may, therefore, effect a similar hormonal response in these patients with cystic fibrosis to those with mucosal damage.
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PMID:Hormonal abnormalities of the pancreas and gut in cystic fibrosis. 700 Jun 12

Increased basal and/or pentagastrin-stimulated gastric acid secretion was observed in 31 of 40 cystic fibrosis (CF) patients as compared to 13 age-matched control volunteers. Fasting serum gastrin level for 20 CF patients of 67.7 +/- 11.1 pg/ml (ranging from 10 to 145 pg/ml) was normal. Meal-stimulated serum gastrin concentrations were not significantly higher for seven CF patients as compared to nine normal subjects. In a rat bioassay, serum extracts from six CF patients produced gastric acid secretion comparable to 250 ng/ml of pentagastrin; significantly (p less than 0.01) greater than the responses produced by serum extracts from six normal subjects. There was no significant correlation of severity of pulmonary disease or steatorrhea with acid secretory results. Fourteen of 16 CF patients biopsied had evidence of proximal small intestinal injury which correlated with basal acid output elevation. Gastric acid hypersecretion in CF patients is due to nongastrin secretagogues and is a cause of proximal small intestinal injury.
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PMID:Gastric acid hypersecretion in cystic fibrosis. 718 68

Pulmonary neuroendocrine cells function as hypoxia-sensitive chemoreceptors, and they release peptides and biogenic amines that are important mediators of pulmonary neonatal adaptation. Some of these products additionally act as autocrine growth factors. Increased numbers of pulmonary neuroendocrine cells have been observed in several smoking-associated pediatric lung disorders such as bronchopulmonary dysplasia, cystic fibrosis, sudden infant death syndrome, and asthma. Disturbed pulmonary neuroendocrine function has been implicated in the etiology of this disease complex. One of the most common smoking-associated lung cancer types, small cell lung carcinoma, expresses phenotypic and functional features of pulmonary neuroendocrine cells. We, as well as others, have shown that the release of the autocrine growth factors 5-hydroxytryptamine (5-HT, serotonin) and mammalian bombesin/gastrin releasing peptide (MB/GRP) by cell lines derived from human small cell lung carcinoma or fetal hamster pulmonary neuroendocrine cells are regulated by a neuronal nicotinic acetylcholine receptor comprised of alpha(7) subunits. In radio-receptor assays, nicotine and the nicotine-derived carcinogenic nitrosamines NNNN. Binding of nicotine or NNK to the alpha(7) receptor resulted in calcium influx and overexpression and activation of the serine-threonine protein kinase Raf-1. In turn, this event lead to overexpression and activation of the mitogen activated (MAP) kinases extracellular signal regulated kinase 1 (ERK1) and extracellular signal regulated kinase 2 (ERK2) and stimulation of DNA synthesis accompanied by an increase in cell numbers in fetal pulmonary neuroendocrine cells and small cell carcinoma cells. Exposure of fetal pulmonary neuroendocrine cells for 6 days to NNK caused a prominant up-regulation of Raf-1. Our findings suggest that chronic exposure to nicotine and NNK in pregnant women who smoke may up-regulate the alpha(7) nicotinic receptor as well as components of its associated mitogenic signal transduction pathway, thus increasing the susceptibilities of the infants for the development of pediatric lung disorders. Similarly, up-regulation of one or several components of this nicotinic receptor pathway in smokers may be an important factor for the development of small cell lung carcinoma.
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PMID:Interaction of tobacco-specific toxicants with the neuronal alpha(7) nicotinic acetylcholine receptor and its associated mitogenic signal transduction pathway: potential role in lung carcinogenesis and pediatric lung disorders. 1077 Oct 23

The duodenum is abnormally acidic in cystic fibrosis (CF) due to decreased bicarbonate ion secretion that is dependent on the CF gene product CFTR. In the CFTR null mouse, the acidic duodenum results in increased signaling from the intestine to the exocrine pancreas in an attempt to stimulate pancreatic bicarbonate ion secretion. Excess stimulation is proposed to add to the stress/inflammation of the pancreas in CF. DNA microarray analysis of the CF mouse revealed altered pancreatic gene expression characteristic of stress/inflammation. When the duodenal pH was corrected genetically (crossing CFTR null with gastrin null mice) or pharmacologically (use of the proton pump inhibitor omeprazole), expression levels of genes measured by quantitative RT-PCR were significantly normalized. It is concluded that the acidic duodenal pH in CF contributes to the stress on the exocrine pancreas and that normalizing duodenal pH reduces this stress.
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PMID:Acidic duodenal pH alters gene expression in the cystic fibrosis mouse pancreas. 1506 29

Multiple cases with various types of pediatric malabsorption syndromes were evaluated. The clinical manifestations, laboratory findings, pathophysiology, and histopathological descriptions of each patient were analyzed in an effort to clear the pathogenesis of the malabsorption syndromes and the treatments were undertaken. The cases studied, included one patient with cystic fibrosis, two with lactose intolerance with lactosuria (Durand type), one with primary intestinal lymphangiectasia, two with familial hypobetalipoproteinemia, one with Hartnup disease, one with congenital chroride diarrhea, one with acrodermatitis enteropathica, one with intestinal nodular lymphoid hyperplasia (NLH), five with intractable diarrhea of early infancy and four with glycogenosis type Ia. Each case description and outcome is described below: 1. A 15-year-old Japanese boy with cystic fibrosis presented with severe symptoms, including pancreatic insufficiency, bronchiectasis, pneumothorax and hemoptysis. His prognosis was poor. Analysis of the CFTR genes of this patient revealed a homozygous large deletion from intron 16 to 17b. 2. In the sibling case of Durand type lactose intolerance, the subjects'disaccaridase activity of the small bowel, including lactase, were within normal limits. The results of per oral and per intraduodenal lactose tolerance tests confirmed lactosuria in both. These observations suggested, not only an abnormal gastric condition, but also duodenal and intestinal mucosal abnormal permeability of lactose. 3. In the case of primary intestinal lymphangiectasia, the subject had a lymphedematous right arm and hand, a grossly coarsened mucosal pattern of the upper gastrointestinal tract (identified via radiologic examination) and the presence of lymphangiectasia (confirmed via duodenal mucosal biopsy). The major laboratory findings were hypoalbuminemia, decreased immunoglobulin levels and lymphopenia resulting from loss of lymph fluid and protein into the gastro-intestinal tract. 4. In two cases of heterozygous familial hypobetalipoproteinemia, serum total cholesterol and betalipoprotein levels were very low. The subjects presented with symptoms and signs of acanthocytosis and fat malabsorption. Further, one subject had neurological abnormalities such as mental retardation and severe convulsions. Treatment with MCT formula diet corrected the lipid malabsorption. 5. A 5-year-old girl presented with pellagra-like rashes, mental retardation and cerebellar ataxia. An oral tryptophan (Trp) and dipeptide (Trp-Phe) loading test were conducted and the renal clearance of amino acids was also evaluated in this patient and in controls. Following the oral Trp loading test, plasma levels of Trp indicated a lower peak in the case, reaching a maximum at 60 minutes. On the other hand, the oral dipeptide (Trp-Phe) loading test in the Hartnup patient showed the peak Trp plasma level was the same as the control subjects. The renal clearance of neutral amino acids in this case increased to levels 5 to 35 times normal. 6. In the case of congenital chloride diarrhea, the subject had secondary lactose intolerance, dehydration, hyponatremia, hypokalemia, hypochloremia, hyperreninemia and metabolic alkalosis. The chloride content of her fecal fluid was very high. The concentrations were 89-103 mEq/l. In contrast, her urine was chloride-free. The subject's growth and development improved after treatment with lactose free formura and oral replacement of the fecal loses of water, NaCl and KCl. Unfortunately, the patient died of a small bowel intussusception. The kidney histopathological finding was juxtaglomerular hyperplasia by a necropsy. 7. In the case of acrodermatitis enteropathica, the subject had characteristic skin lesions, low serum zinc levels and ALPase activity. An oral ZnSO4 loading test and intestinal mucosal histology by a peroral biopsy were conducted. The serum zinc peak level was 2 hours after the oral ZnSO4 loading test. Infant formula alone could not maintain normal serum zinc ranges. Light microscopic studies of the intestinal villous architecture showed a normal pattern. However, ultrastructual examination of several epithelial cells revealed numerous intracellular vesicles. After zinc therapy, these changes were decreased. The lesions were postulated as the secondary result of zinc deficiency. 8. A 12-year-old girl presented with hypogammaglobulinemia, recurrent infections, chronic diarrhea and intestinal NLH. A barium meal and follow-through examination showed multiple nodules throughout the stomach and intestine. The nodules, all uniform in size, were 2 mm diameter. The barium enema did not show NLH in the colon. Mucosal biopsy of the stomach and jejunum revealed the typical histology of NLH in the lamina propria. Also, achlorhydria was present in this patient and her serum gastrin levels were very high; 315-775 pg/ml. 9. In 4 cases of intractable diarrhea in early infancy (by Avery G B), a jejunal biopsy showed shortening villi and nonspecific enterocolitis. Some patients were found with only low lactase or low lactase and sucrase levels. An electron microscope analysis of the small bowel in 2 cases showed alterations: increased pinocytosis in microvillus membranes and lysosomes by endocytosis of undigested macromolecular substances. I postulated that the stated evidence was causative of this clinical profile. 10. I frequently observed diarrhea as a clinical manifestation in glycogenosis type Ia and lipid malabsorption in one case. The light and electron photomicrographs showed intestinal absorption cells with the glycogen deposits in the inferior devision of nuclei.
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PMID:[Clinical studies of pediatric malabsorption syndromes]. 1722 86

In their seminal papers Hanahan and Weinberg described oncogenic processes a normal cell undergoes to be transformed into a cancer cell. The functions of ion channels in the gastrointestinal (GI) tract influence a variety of cellular processes, many of which overlap with these hallmarks of cancer. In this review we focus on the roles of the calcium (Ca2+), sodium (Na+), potassium (K+), chloride (Cl-) and zinc (Zn2+) transporters in GI cancer, with a special emphasis on the roles of the KCNQ1 K+ channel and CFTR Cl- channel in colorectal cancer (CRC). Ca2+ is a ubiquitous second messenger, serving as a signaling molecule for a variety of cellular processes such as control of the cell cycle, apoptosis, and migration. Various members of the TRP superfamily, including TRPM8, TRPM7, TRPM6 and TRPM2, have been implicated in GI cancers, especially through overexpression in pancreatic adenocarcinomas and down-regulation in colon cancer. Voltage-gated sodium channels (VGSCs) are classically associated with the initiation and conduction of action potentials in electrically excitable cells such as neurons and muscle cells. The VGSC NaV1.5 is abundantly expressed in human colorectal CRC cell lines as well as being highly expressed in primary CRC samples. Studies have demonstrated that conductance through NaV1.5 contributes significantly to CRC cell invasiveness and cancer progression. Zn2+ transporters of the ZIP/SLC39A and ZnT/SLC30A families are dysregulated in all major GI organ cancers, in particular, ZIP4 up-regulation in pancreatic cancer (PC). More than 70 K+ channel genes, clustered in four families, are found expressed in the GI tract, where they regulate a range of cellular processes, including gastrin secretion in the stomach and anion secretion and fluid balance in the intestinal tract. Several distinct types of K+ channels are found dysregulated in the GI tract. Notable are hERG1 upregulation in PC, gastric cancer (GC) and CRC, leading to enhanced cancer angiogenesis and invasion, and KCNQ1 down-regulation in CRC, where KCNQ1 expression is associated with enhanced disease-free survival in stage II, III, and IV disease. Cl- channels are critical for a range of cellular and tissue processes in the GI tract, especially fluid balance in the colon. Most notable is CFTR, whose deficiency leads to mucus blockage, microbial dysbiosis and inflammation in the intestinal tract. CFTR is a tumor suppressor in several GI cancers. Cystic fibrosis patients are at a significant risk for CRC and low levels of CFTR expression are associated with poor overall disease-free survival in sporadic CRC. Two other classes of chloride channels that are dysregulated in GI cancers are the chloride intracellular channels (CLIC1, 3 & 4) and the chloride channel accessory proteins (CLCA1,2,4). CLIC1 & 4 are upregulated in PC, GC, gallbladder cancer, and CRC, while the CLCA proteins have been reported to be down-regulated in CRC. In summary, it is clear, from the diverse influences of ion channels, that their aberrant expression and/or activity can contribute to malignant transformation and tumor progression. Further, because ion channels are often localized to the plasma membrane and subject to multiple layers of regulation, they represent promising clinical targets for therapeutic intervention including the repurposing of current drugs.
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PMID:Role of ion channels in gastrointestinal cancer. 3163 70


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