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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By means of histochemical methods it was established that carboanhydrase of the parietal cells of fundal glands and HCO-3 stimulated ATP-ase of the rat's gastric mucosa capillaries disposed next to the parietal cells were activated by food and histamine. The obtained data confirm the idea of the multicellular functional essembly sustaining HCL secretion (R. I. Salganik, 1974). Should gastrin induce the formation of histamine in endocrinous cells and the histamine activate carboanhydrase in parietal cells, our data confirm the supposition that HCO-3-ions stimulate ATP-ase sustaining the exchange between HCO-3-cells and C1- of blood to form HCl in the endothelial cells of blood capillaries adjacent to the parietal cells.
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PMID:[Histochemical study of carbonic anhydrase and HCO3(-)-stimulated adenosine triphosphatase in the rat stomach during hydrochloric acid secretion]. 13 Aug 54

Secretagogues of pancreatic enzyme secretion, the hormones pancreozymin, carbamylcholine, gastrin I, the octapeptide of pancreozymin, and caerulein as well as the Ca++ -ionophore A 23187 stimulate 45Ca efflux from isolated pancreatic cells. The non-secretagogic hormones adrenaline, isoproterenol, secretion, as well as dibutyryl cyclic adenosine 3',5'-monophosphate and dibutyryl cyclic guanosine 3',5'-monophosphate have no effect on 45Ca efflux. Atropine blocks the stimulatory effect of carbamylcholine on 45Ca efflux complately, but not that of pancreozymin. A graphical analysis of the Ca++ efflux curves reveals at least three phases: a first phase, probably derived from Ca++ bound to the plasma membrane; a second phase, possibly representing Ca++ efflux from cytosol of the cells; and a third phase, probably from mitochondria or other cellular particles. The Ca++ efflux of all phases is stimulated by pancreozymin and carbamylcholine. Ca++ efflux is not significantly effected by the presence or absence of Ca++ in the incubation medium. Metabolic inhibitors of ATP production. Antimycin A and dinitrophenol, which inhibit Ca++ uptake into mitochondria, stimulate Ca++ efflux from the isolated cells remarkably, but inhibit the slow phase of Ca++ influx, indicating the role of mitochondria as an intracellular Ca++ compartment. Measurements of the 45Ca++ influx at different Ca++ concentrations in the medium reveal saturation type kinetics, which are compatible with a carrier or channel model. The hormones mentioned above stimulate the rate of Ca++ translocation. The data suggest that secretagogues of pancreatic enzyme secretion act by increasing the rate of Ca++ transport most likely at the level of the cell membrane and that Ca++ exchange diffusion does not contribute to the 45Ca++ fluxes.
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PMID:Ca++ fluxes in isolated cells of rat pancreas. effect of secretagogues and different Ca++ concentrations. 78 85

In cultures of Escherichia coli W4597(K) and G34 under various nutritional conditions the rates of glucose utilization and cellular levels of fructose-1,6-P2 are quantitatively related by the Hill equation where the value of the Hill coefficient is approximately equal to 2. This is the first evidence that fructose-P2, or any metabolite which covaries with fructose-P2, modulates glucose utilization in E. coli. In light of previous observations from our laboratory this new observation and those in the succeeding report provide the first evidence that in E. coli glycolysis, glycogen synthesis and glucose utilization are coordinately regulated, thus providing for the coupling of ATP utilization and production under various metabolic circumstances. Alterations in the level of ATP apparently affect the velocity of phosphofructokinase, the rate-limiting enzyme in glycolysis, altering the cellular levels of glucose-6-P or fructose-P2. Changes in the levels of these hexose phosphates are quantitatively related to alterations in the rates of glucose utilization and glycogen synthesis in the intact E. coli cell.
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PMID:Evidence for the coordinate control of glycogen synthesis, glucose utilization, and glycolysis in Escherichia coli. I. Quantitative covariance of the rate of glucose utilization and the cellular level of fructose 1,6-diphosphate during exponential growth and nutrient limitation. 110 Jun 22

In cultures of Escherichia coli W4597(K) and G34 under various nutritional conditions the rates of glucose utilization and cellular levels of fructose-1,6-P2 are quantitatively related by the Hill equation where the value of the Hill coefficient is approximately equal to 2. This is the first evidence that fructose-P2, or any metabolite which covaries with fructose-P2, modulates glucose utilization in E. coli. In light of previous observations from our laboratory this new observation and those in the succeeding report provide the first evidence that in E. coli glycolsis, glycogen synthesis and glucose utilization are coordinately regulated, thus providing for the coupling of ATP utilization and production under various metabolic circumstances. Alterations in the level of ATP apparently affect the velocity of phosphofructokinase, the rate-limiting enzyme in glycolsis, altering the cellular levels of glucose-6-P or fructose-P2. Changes in the levels of these hexose phosphates are quantitatively related to alterations in the rates of glucose utilization and glycogen synthesis in the intact E. coli cell.
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PMID:Evidence for the coordinate control of glycogen synthesis, glucose utilization, and glycolysis in Escherichia coli. II. Quantitative correlation of the inhibition of glycogen synthesis and the stimulation of glucose utilization by 2,4-dinitrophenol with the effects on the cellular levels of glucose 6-phosphate, fructose, 1,6-diphosphate, and total adenylates. 110 Jun 23

Many studies suggest that smooth muscle relaxation caused by beta-adrenergic agents and various neuropeptides occurs as a result of an increase in cellular adenosine 3',5'-cyclic monophosphate (cAMP). However, the evidence is indirect, and furthermore does not demonstrate that an increase in cAMP is essential for mediating relaxation. To define more clearly the role of cAMP in receptor-mediated smooth muscle relaxation, we used a specific competitive antagonist of the action of cAMP on protein kinase A, (R)-p-adenosine 3',5'-cyclic phosphorothioate [(R)-p-cAMPS], and its S isomer, (S)-p-cAMPS, which functions as a cAMP agonist. In gastric smooth muscle cells from guinea pig, (S)-p-cAMPS caused a dose-related relaxation [50% inhibitory concentration (IC50) 86 +/- 59 nM]. Vasoactive intestinal peptide (VIP) produced smooth muscle cell relaxation (IC50 2.3 +/- 0.8 nM) through occupation of specific VIP receptors. (R)-p-cAMPS inhibited VIP-induced relaxation, with a rightward shift in the VIP dose-response curve, suggesting competitive antagonism. Furthermore, (R)-p-cAMPS inhibited relaxation induced by other agents that increase cellular cAMP (isoproterenol, calcitonin gene-related peptide, and glucagon) but not that induced by ATP or sodium nitroprusside. (R)-p-cAMPS had no effect on contraction stimulated by carbachol, cholecystokinin, or substance P. These data demonstrate that activation of protein kinase A is primarily responsible for mediating gastrin smooth muscle relaxation produced by adrenergic agents and various neuropeptides.
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PMID:A primary role for protein kinase A in smooth muscle relaxation induced by adrenergic agonists and neuropeptides. 132 27

The regulation of acid secretion was clarified by the development of H2-receptor antagonists in the 1970s. It appears that gastrin and acetylcholine exert their effects on acid secretion mainly by stimulation of histamine release from the enterochromaffin-like (ECL) cell of the fundic gastric mucosa. The isolated ECL cell of rat gastric mucosa responds to gastrin/cholecystokinin (CCK), acetylcholine, and epinephrine with histamine release and to somatostatin and R-alpha-methyl histamine by inhibition of histamine release. Histamine and acetylcholine stimulate the parietal cell by elevation of cAMP or [Ca]i by activation of H2 or M3 receptors, respectively. These independent pathways converge to activate the gastric acid pump, the H+,K+ ATPase. Activation is a function of the association of the ATPase with a potassium chloride transport pathway that occurs in the membrane of the secretory canaliculus of the parietal cell. Hence the secretory canaliculus is the site of acid secretion, the acid being pumped into the lumen of the canaliculus. The pump is composed of two subunits, a large catalytic and a smaller glycosylated protein. This final step of acid secretion has become the target of drugs also designed to inhibit acid secretion. The target domain of the benzimidazole class of acid pump inhibitors is the extracytoplasmic domain of the pump that is secreting acid, and the target amino acids are the cysteines present in this domain. The secondary structure of the pump can be analyzed by determining trypsin-sensitive bonds in intact, cytoplasmic-side-out vesicles of the ATPase, and it has been shown that the alpha subunit has at least eight membrane-spanning segments. Omeprazole, the first acid pump inhibitor, forms a disulfide bond with cysteines in the extracytoplasmic loop between the fifth and sixth membrane-spanning segment and to a cysteine in the extracytoplasmic loop between the seventh and eight segments, preventing phosphorylation of the pump by ATP. As a result of the effective and long-lasting inhibition of acid secretion by the acid pump inhibitor, superior clinical results have been found in all forms of acid-related disease.
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PMID:Acid secretion and the H,K ATPase of stomach. 134 Oct 65

Specific binding sites for human gastrin I (gastrin) were identified in a crude membrane preparation from the gastric carcinoid tumor of Mastomys (Praomys) natalensis. The binding of 125I-gastrin to the carcinoid tumor membrane was saturable, and Scatchard analysis of the data revealed a single class of binding site with a dissociation constant of 139.2 pM and a maximal binding capacity of 23.5 fmol/mg protein. Gastrin and CCK8 equipotently and dose-dependently displaced the binding of 125I-gastrin to the membrane. GTP but not ATP decreased 125I-gastrin binding to the membrane, and removal of Mg2+ attenuated this inhibitory action of GTP. The GTP-induced reduction of 125I-gastrin binding was found to be due to a decrease in binding affinity without a change in binding capacity. These results clearly indicate the presence of specific binding sites for gastrin, probably coupled to guanine nucleotide-binding protein, in the carcinoid tumor membrane of Mastomys, and suggest that gastrin has possible biological actions on these tumors.
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PMID:Receptors for gastrin on gastric carcinoid tumor membrane of Mastomys natalensis. 204 96

Two gastrin analogs containing a D- and a L-tetrafluorinated tyrosyl residue (Arg-Arg-Leu-Glu-Glu-Glu-Glu-Glu-Ala-(F4)Tyr-Gly) were synthesized and tested as substrates and inhibitors of the insulin receptor kinase. No phosphorylation of these peptides was observed, but both gastrin analogs were effective inhibitors in the microM range. Although the D- and L-tetrafluorotyrosine-gastrin analogs differ in the sequence by only 1 amino acid residue, a different inhibitory pattern was obtained with the insulin receptor. The inhibition of all-L-isomer is competitive with respect to both the protein substrate, reduced, S-carboxymethylated, and maleylated lysozyme (RCMM-lysozyme), and ATP with a Ki value of 4 microM. This result corroborates a previous finding (Walker, D. H., Kuppuswamy, D., Visvanathan, A., and Pike, L. J. (1987) Biochemistry 26, 1428-1433) that the kinetic mechanism for insulin receptor is a random Bi Bi mechanism. Different from the L-isomer, the D-analog is competitive to RCMM-lysozyme and noncompetitive toward ATP and gives an apparent inhibition constant of 20 microM. A free tetrafluorotyrosine also shows a competitive inhibition to protein substrate, RCMM-lysozyme (Ki = 18 mM) whereas free tyrosine shows no effect on the activity of insulin receptor. These results show the importance of the charge state and nucleophilicity of the phenolic component in substrate recognition and catalysis and provide a rationale for the design of inhibitors of tyrosyl phosphorylation.
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PMID:A rationale for the design of an inhibitor of tyrosyl kinase. 216 84

The effect of self-phosphorylation on the protein-tyrosine kinase activity of the epidermal growth factor receptor has been investigated using immunoaffinity-purified protein. Enzyme was first incubated for various times with excess ATP to phosphorylate it to differing extents; the ability of the enzyme to phosphorylate exogenous peptide substrates was then measured as a function of its self-phosphorylation state. Increasing self-phosphorylation to 1.3-1.8 mol of phosphate mol-1 of epidermal growth factor receptor enhanced protein-tyrosine kinase activity 2-3-fold. Comparison of the kinetics of protein-tyrosine kinase activity at different ATP concentrations revealed significant differences between unphosphorylated and phosphorylated enzyme. At low levels of ATP, a double reciprocal plot of the protein-tyrosine kinase activity of the unphosphorylated enzyme was hyperbolic, suggesting that ATP may act as an activator of the enzyme. At higher ATP concentrations, where greater levels of self-phosphorylation occurred during the reaction, the kinetics appeared linear and similar to those of the phosphorylated enzyme. Dose-response studies using three different peptide substrates (angiotensin II, gastrin, and a synthetic peptide corresponding to the self-phosphorylation site in p60v-src) showed that exogenous substrates inhibit receptor self-phosphorylation. In each case, half-maximal inhibition was observed at a peptide concentration approximately equal to the substrate's Km. A kinetic analysis comparing peptide phosphorylation using unphosphorylated and prephosphorylated enzyme indicated that the self-phosphorylation site can act as a competitive inhibitor (alternate substrate) versus peptide substrates. These results suggest that self-phosphorylation of the epidermal growth factor receptor removes a competitive constraint so that exogenous substrates can be more readily phosphorylated.
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PMID:Self-phosphorylation enhances the protein-tyrosine kinase activity of the epidermal growth factor receptor. 299 17

The parietal cells possess the unique capacity to produce large quantities of acid at a high concentration, and this is reflected in unique properties at the cellular level. The cells are comparatively large, and they are equipped with secretory canaliculi, a multitude of mitochondria, and cytoplasmic tubulovesicles. During secretion many of the tubulovesicles merge with the secretory canaliculi, which then expand. In the process H+, K+-ATPase is transferred from the tubulovesicular membrane to the secretory membrane. This enzyme catalyses the final step in the production of HCl. Parietal cell activity is regulated through receptors on the basolateral cell surfaces. In the isolated gland and in the isolated parietal-cell fractions, stimulation of receptors for histamine evokes higher secretion than receptor stimulation with cholinergic compounds or with gastrin. In these experimental models, specific inhibitors are required to block acid secretion; for example histamine H2-receptor antagonists will block histamine-induced secretion but will be inactive when secretion is evoked by gastrin or by cholinergic stimulation. These stimuli cause a more or less marked increase in the intracellular levels of Ca2+, which acts as a second messenger, leading to the activation of phosphokinases and, ultimately, to morphological transformation of the parietal cells and acid secretion. Another such intracellular messenger is cAMP, which is formed in response to histamine stimulation only; prostaglandins may prevent this process and block acid secretion. The final step in the production of acid requires K+ and Cl- channels in the secretory membrane and the H+, K+-ATPase-catalysed exchange of K+ for H+ across this membrane. This reaction consumes large amounts of energy and depends on the aerobic production of ATP by the parietal cells. Substituted benzimidazoles, such as omeprazole, accumulate in the acid compartments of the parietal cells and inhibit the H+, K+-ATPase, thereby blocking acid production.
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PMID:Physiology and pharmacology of the parietal cell. 304 49


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