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)

Gastrin, somatostatin, H+/K(+)-ATPase and carbonic anhydrase are principal elements of acid secretion. We investigated in the conscious sheep the effect of 24 h omeprazole (an H+/K(+)-ATPase inhibitor) infusion on these elements at the level of synthesis, storage and secretion. Omeprazole inhibited acid secretion-pH increased from 3.0 to 7.1 at 24 h. Plasma amidated and glycine extended gastrin increased 3-fold while the ratio of amidated to glycine extended gastrins (4:1) remained unchanged. Despite the increase in circulating gastrin, antral gastrin concentration and mRNA did not change significantly. Gastrin-17 (amidated and glycine extended) was the predominant form in the circulation and antrum, although there were preferential increases in larger forms following omeprazole treatment. Omeprazole had no effect on somatostatin mRNA or peptide levels in the fundus. Similarly, plasma somatostatin remained unchanged. However, antral somatostatin increased significantly (63%) following omeprazole treatment accompanied by a 4-fold increase in its mRNA. Fundic H+/K(+)-ATPase mRNA was unchanged but a significant increase (87%) in carbonic anhydrase II mRNA was observed. Omeprazole induced hypergastrinaemia occurred without a measurable reduction in storage or increased synthesis of gastrin at 24 h. Increased antral somatostatin synthesis and storage may result from stimulation by plasma gastrin on antral D cells, independent of acid. The rise in carbonic anhydrase II mRNA in the absence of any change in H+/K(+)-ATPase mRNA may reflect the differential sensitivity of the genes encoding these two enzymes to the stimulatory action of gastrin.
 ...
PMID:Achlorhydria induced changes in gastrin, somatostatin, H+/K(+)-ATPase and carbonic anhydrase in the sheep. 135 10

Carbamoylcholine (carbachol), histamine, and gastrin are three principal stimulants of gastric acid secretion. To explore the mechanisms by which these agents exert their actions in parietal cells, we examined their effects on the gene expression of the enzymes responsible for H+ generation. Each secretagogue induced rapid and coordinate increases in steady-state levels of mRNAs encoding carbonic anhydrase II and H+,K+-ATPase in isolated canine gastric parietal cells. Furthermore, pronounced increases, with different kinetics, in expression of beta-actin mRNA were observed. With increasing time after cell isolation, carbonic anhydrase II and H+,K+-ATPase, but not beta-actin, mRNA levels were attenuated, suggesting that parietal cell-specific genes may be dependent upon maintenance of parietal cell contacts within intact mucosal tissue. Pretreatment of the cells with competitive inhibitors of each secretagogue blocked the increases. Our results indicate that acid secretagogue-specific receptor activation in parietal cells triggers coordinate gene expression of the two enzymes involved in H+ ion generation and that beta-actin may be an important regulator of acid secretion.
 ...
PMID:Acid secretagogue-induced stimulation of gastric parietal cell gene expression. 254 91

The activity of gastric parietal cells in terms of hydrochloric acid (HCl) secretion is regulated by the interaction of stimulatory substances (e.g. gastrin) and inhibitors (e.g. somatostatin) acting in an endocrine and paracrine mode, as well as luminal factors. In the present study the following parameters were measured: the synthesis (mRNA), storage (tissue peptide concentration) and secretion (plasma peptide concentration) of somatostatin and gastrin following short-term treatment of rats with pentagastrin (acid stimulant), secretin, omeprazole (reduces gastric acidity by inactivating gastric H/K ATPase) and the somatostatin analogue octreotide (reduces gastric acidity by inhibiting both the parietal cell and gastrin). The mRNA coding for H/K ATPase and carbonic anhydrase II (CA II), the two enzymes responsible for the generation of hydrogen ions from the parietal cell, were also quantitated. In response to octreotide, somatostatin peptide and mRNA levels in the fundus rose to 180 +/- 16% (P < 0.001) and 1073 +/- 356% (P < 0.05) of control, respectively. In contrast, octreotide caused a decrease in antral somatostatin peptide and its mRNA did not change significantly. No significant changes in synthesis, secretion or storage of gastrin were observed except for omeprazole induced hypergastrinaemia (580 +/- 76%, P < 0.001). H/K ATPase and CA II mRNA were largely unaffected except for an increase in CA II mRNA following octreotide and a decrease in H/K ATPase mRNA after pentagastrin. These data support the concept of the differential control of antral and fundic somatostatin synthesis and provide evidence for a regulatory loop by which somatostatin can influence its own synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Secretory and biosynthetic responses of gastrin and somatostatin to acute changes in gastric acidity. 852 6

Significant advances in intestinal stem cell biology have been made in murine models; however, anatomical and physiological differences between mice and humans limit mice as a translational model for stem cell based research. The pig has been an effective translational model, and represents a candidate species to study intestinal epithelial stem cell (IESC) driven regeneration. The lack of validated reagents and epithelial culture methods is an obstacle to investigating IESC driven regeneration in a pig model. In this study, antibodies against Epithelial Adhesion Molecule 1 (EpCAM) and Villin marked cells of epithelial origin. Antibodies against Proliferative Cell Nuclear Antigen (PCNA), Minichromosome Maintenance Complex 2 (MCM2), Bromodeoxyuridine (BrdU) and phosphorylated Histone H3 (pH3) distinguished proliferating cells at various stages of the cell cycle. SOX9, localized to the stem/progenitor cells zone, while HOPX was restricted to the +4/'reserve' stem cell zone. Immunostaining also identified major differentiated lineages. Goblet cells were identified by Mucin 2 (MUC2); enteroendocrine cells by Chromogranin A (CGA), Gastrin and Somatostatin; and absorptive enterocytes by carbonic anhydrase II (CAII) and sucrase isomaltase (SIM). Transmission electron microscopy demonstrated morphologic and sub-cellular characteristics of stem cell and differentiated intestinal epithelial cell types. Quantitative PCR gene expression analysis enabled identification of stem/progenitor cells, post mitotic cell lineages, and important growth and differentiation pathways. Additionally, a method for long-term culture of porcine crypts was developed. Biomarker characterization and development of IESC culture in the porcine model represents a foundation for translational studies of IESC-driven regeneration of the intestinal epithelium in physiology and disease.
...
PMID:Cell lineage identification and stem cell culture in a porcine model for the study of intestinal epithelial regeneration. 2384 Apr 80