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)

Proglumide has been shown to be an in vivo inhibitor of secretagogue-stimulated gastric acid secretion. In the present study, we have examined the ability of proglumide and benzotript, a new tryptophan derivative, to inhibit acid output from isolated gastric fundic parietal cells from rabbit. As measured with the [14C]aminopyrine (AP) accumulation method as an index of acid secretion, the two drugs inhibited basal AP with IC-50 values of 1 X 10(-2) M for proglumide and 1 X 10(-3) M for benzotript. In the case of secretagogue stimulation (1) benzotript slightly affected histamine-induced AP (15% inhibition at 5 X 10(-3) M), proglumide did not; (2) both proglumide and benzotript inhibited in a non-competitive manner acetylcholine-induced AP; (3) these isolated cells were sensitive to gastrin and the dose-response curve for the stimulant was biphasic (maximum for 1 X 10(-9) M), suggesting a desensitization mechanism. Proglumide and benzotript competitively inhibited both [125I]gastrin binding to its receptor sites and gastrin-induced AP, suggesting they are members of a class of gastrin-receptor antagonists. But, this suggestion cannot exclude other post-receptorial mechanisms involved in the acid output from parietal cells.
 ...
PMID:Evidence that proglumide and benzotript antagonize secretagogue stimulation of isolated gastric parietal cells. 632 Mar 14

Individual l-amino acids were instilled intragastrically to determine possible differences in stimulation of gastric acid secretion and gastrin and pancreatic polypeptide release. Phenylalanine and tryptophan were significantly more potent stimulants of gastric acid secretion and of pancreatic polypeptide and gastrin release than any of the other amino acids tested. Smaller, but significant, responses were obtained with threonine for pancreatic polypeptide and with serine for acid secretion. We conclude that a major part of the acid-stimulating action of mixed amino acid solution can be explained by the aromatic amino acids, phenylalanine and tryptophan, which are also the most potent stimulants of gastrin and pancreatic polypeptide release. These studies suggest that the specific composition of amino acid mixtures determines the net effects of such mixtures on gastric secretion, and on release of both the antral hormone gastrin and the pancreatic hormone, pancreatic polypeptide.
 ...
PMID:Effect of individual l-amino acids on gastric acid secretion and serum gastrin and pancreatic polypeptide release in humans. 680 40

To determine whether intravenous infusion of individual amino acids stimulated gastric acid secretion in man, graded doses of phenylalanine, tryptophan, glycine, alanine, histidine, and NaCl control were infused on separate days in nine healthy subjects. Intravenous infusion of phenylalanine and tryptophan significantly stimulated gastric acid secretion to 50 and 52%, respectively, of the acid secretory response to intragastric peptone. Intravenous alanine and histidine were without effect, whereas glycine produced a slight response. Serum gastrin concentrations did not significantly change during intravenous amino acid infusion, except in response to 0.1 M phenylalanine. However, the increase in serum gastrin occurred 2 h after acid secretion had significantly increased in response to the 0.025 M phenylalanine infusion. Plasma amino acid concentrations were measured during intravenous amino acid infusion and in response to a steak meal in five of the subjects. At a time when acid secretion was significantly increased during intravenous infusion of phenylalanine and tryptophan, plasma amino acids were similar to, or less than, that observed after the steak meal, suggesting that circulating levels of these three amino acids have a physiologic effect on gastric secretion in man. Intravenous infusion of a combination of graded doses of phenylalanine plus a continuous infusion of 0.01 M tryptophan shifted the dose-response curve to the left and resulted in a significantly greater response than to either amino acid alone. In five subjects with parietal cell vagotomy, intravenous phenylalanine and tryptophan stimulated acid secretion, whereas histidine was without effect, similar to normal subjects. These studies indicate that intravenous infusion of small amounts of phenylalanine (0.025 M, 3.1 mmol/h) and tryptophan (0.01 M, 1.25 mmol/h) stimulated gastric acid secretion at plasma concentrations similar to those observed after a steak meal, suggesting a physiologic role for circulating levels of these amino acids on gastric acid secretion. Because acid secretion increased at a time when serum gastrin was unchanged and since there was no correlation between changes in serum gastrin and acid secretion, the responses to phenylalanine and tryptophan are probably mediated by a nongastrin-related mechanism(s). Since both phenylalanine and tryptophan stimulated secretion in vagotomized subjects, the response is vagally independent. These observations suggest that circulating levels of these two amino acids have either a direct or indirect effect on or near the human parietal cell.
 ...
PMID:Intravenous infusion of L-isomers of phenylalanine and tryptophan stimulate gastric acid secretion at physiologic plasma concentrations in normal subjects and after parietal cell vagotomy. 685 13

Twenty-six peptides, analogs of bombesin (BNa) and gastrin releasing peptide (GRP), have been synthesized by the solid phase method. The synthetic peptides were purified by ion exchange and partition chromatography and shown to be homogenous under various conditions on RP-HPLC. They were further characterized by TLC, amino acid analysis and optical rotation. These peptides have been administered IC to rats and their effects on thermoregulation and glucoregulation have been compared to those of the two natural peptides: frog skin bombesin (BNa) and GRP. Their structure activity relationship is also discussed. The minimum essential residues required for full potency of bombesin-like effects is represented by an acetylated C-terminal 8-peptide fragment, where in position 7 of this peptide an L-amino acid such as alanine, histidine or glutamine, or the D-glutamine residue can be introduced. Modification of the tryptophan [8] and histidine [12] residues by alanine abolished the biological potency of those peptides. Analogs with a free N-terminus were found to express little, but significant, activity, thus indicating that blocked N-terminus is necessary for maximal response. [Ac-Ala7, DAla11]-bombesin (7--14) and [Ac-DGln7 DAla11]-bombesin (7--14) were found to be more potent than bombesin, whereas [Ac-DAla7, DAla11]-bombesin or [Ac-DAla7, DAla11] bombesin N-methylamide were found to have 10 and 1% of bombesin potency, respectively.
 ...
PMID:Bombesin analogs: effects on thermoregulation and glucose metabolism. 734 58

A Haemophilus influenzae type-b capsular polysaccharide-CRM197 protein conjugate vaccine was compared with unconjugated CRM197 and diphtheria toxin, its parent molecule. Using CD and fluorescence spectroscopy, it has been possible to observe differences in structure and stability to pH and temperature due to the G52-->E mutation in CRM197 and the 'glycosylation' of CRM197 in the conjugate. CRM197 resembles the 'open' conformation of diphtheria toxin [Blewitt, M. G., Chung, L. A. & London, E. (1985) Biochemistry 24, 5458-5464] and the attachment of poly(ribosyl-ribitol phosphate) carbohydrate chains results in a still 'more open' state, although only a small decrease in the amount of ordered structure was observed. Fluorescence spectra of gel-filtration column fractions of the conjugate suggest that material of higher apparent molecular size is in the 'more open' conformation. Conjugated CRM197 begins unfolding at slightly lower temperatures (25-35 degrees C) than native material (> 35 degrees C). In the conjugate, tryptophan residues are more accessible to the non-ionic fluorescence quencher acrylamide at 35 degrees C. The conformational change observed at pH4-6 for diphtheria toxin is also observed for CRM197, but in the conjugate begins at higher pH. This may result from the presence of charged oligosaccharide residues on the surface or the conjugation methods used. The consequences of these changes in conformation and solution behaviour of the carrier protein in terms of its ability to induce a protective, T-cell-dependent response to H. influenzae polysaccharide remain to be determined.
 ...
PMID:Comparison of the diphtheria mutant toxin, CRM197, with a Haemophilus influenzae type-b polysaccharide-CRM197 conjugate by optical spectroscopy. 920 20

Melatonin, a pineal hormone, synthesized from L-tryptophan, is known to exist in the gut and to scavenge oxygen free radicals but its role in gastroprotection against acute lesions induced by various strong irritants has been little studied. In this study, we determined the effects of melatonin and L-tryptophan on gastric secretion and the formation of acute gastric lesions induced by absolute ethanol, acidified aspirin (ASA), stress, and ischemia-reperfusion (I/R). Area of gastric lesions was determined by planimetry, gastric blood flow (GBF) was measured using a H2-gas clearance technique, and blood was withdrawn for the measurement of free radicals, plasma gastrin, and melatonin concentration by specific radioimmunoassay. Intragastric (i.g.) administration of melatonin (2.5-10 mg/kg) or L-tryptophan (25-200 mg/kg) failed to affect gastric lesions by ethanol and ASA but dose-dependently reduced the lesions provoked by stress and I/R; this protective effect was accompanied by a significant rise in plasma melatonin level, GBF, and DNA synthesis and by a marked fall in blood free radicals. L-tryptophan, which significantly elevated the plasma melatonin by about 3-5-fold, also reduced the stress and I/R-induced lesions and blood levels of free radicals, while increasing the GBF, DNA synthesis, and plasma gastrin levels. Inhibition of mucosal generation of PGE2 by indomethacin abolished the protection and the rise of GBF afforded by melatonin and L-tryptophan, whereas pretreatment with N(G)-nitro-L-arginine (L-NNA), to suppress nitric oxide (NO) synthase, was without any effect. We conclude that melatonin applied exogenously in pharmacological doses and that released by the administration of its precursor, L-tryptophan, protect gastric mucosa from the damage induced by stress and I/R possibly by a mechanism involving the scavenging of free radicals and gastric hyperemia probably mediated by endogenous prostaglandin but not NO.
 ...
PMID:The role of melatonin and L-tryptophan in prevention of acute gastric lesions induced by stress, ethanol, ischemia, and aspirin. 939 46

The wild-type transcript of Escherichia coli tRNASec, characterized by a peculiar core architecture and a large variable region, was shown to be aspartylatable by yeast AspRS. Similar activities were found for tRNASec mutants with methionine, leucine, and tryptophan anticodons. The charging efficiency of these molecules was found comparable to that of a minihelix derived from tRNAAsp and is accounted for by the presence of the discriminator residue G73, which is a major aspartate identity determinant. Introducing the aspartate identity elements from the anticodon loop (G34, U35, C36, C38) into tRNASec transforms this molecule into an aspartate acceptor with kinetic properties identical to tRNAAsp. Expression of the aspartate identity set in tRNASec is independent of the size of its variable region. The functional study was completed by footprinting experiments with four different nucleases as structural probes. Protection patterns by AspRS of transplanted tRNASec and tRNAAsp were found similar. They are modified, particularly in the anticodon loop, upon changing the aspartate anticodon into that of methionine. Altogether, it appears that recognition of a tRNA by AspRS is more governed by the presence of the aspartate identity set than by the structural framework that carries this set.
 ...
PMID:The peculiar architectural framework of tRNASec is fully recognized by yeast AspRS. 1019 66

1. Gastrin stimulates rat stomach ECL cells to secrete histamine and pacreastatin, a chromogranin A (CGA)-derived peptide. The present report describes the effect of nine cholecystokinin2 (CCK2) receptor antagonists and one CCK1 receptor antagonist on the gastrin-evoked secretion of pancreastatin from isolated ECL cells. 2. The CCK2 receptor antagonists comprised three benzodiazepine derivatives L-740,093, YM022 and YF476, one ureidoacetamide compound RP73870, one benzimidazole compound JB 93182, one ureidoindoline compound AG041R and three tryptophan dipeptoids PD 134308 (CI988), PD135158 and PD 136450. The CCK1 receptor antagonist was devazepide. 3. A preparation of well-functioning ECL cells (approximately 80% purity) was prepared from rat oxyntic mucosa using counter-flow elutriation. The cells were cultured for 48 h in the presence of 0.1 nM gastrin; they were then washed and incubated with antagonist alone or with various concentrations of antagonist plus 10 nM gastrin (a maximally effective concentration) for 30 min. Gastrin dose-response curves were constructed in the absence or presence of increasing concentrations of antagonist. The amount of pancreastatin secreted was determined by radioimmunoassay. 4. The gastrin-evoked secretion of pancreastatin was inhibited in a dose-dependent manner. YM022, AG041R and YF476 had IC50 values of 0.5, 2.2 and 2.7 nM respectively. L-740,093, JB93182 and RP73870 had IC50 values of 7.8, 9.3 and 9.8 nM, while PD135158, PD136450 and PD134308 had IC50 values of 76, 135 and 145 nM. The CCK1 receptor antagonist devazepide was a poor CCK2 receptor antagonist with an IC50 of about 800 nM. 5. YM022, YF476 and AG041R were chosen for further analysis. YM022 and YF476 shifted the gastrin dose-response curve to the right in a manner suggesting competitive antagonism, while the effects of AG041R could not be explained by simple competitive antagonism. pK(B) values were 11.3 for YM022, 10.8 for YF476 and the apparent pK(B) for AG041R was 10.4.
 ...
PMID:Pharmacological analysis of CCK2 receptor antagonists using isolated rat stomach ECL cells. 1038 55

A 78 kDa gastrin-binding protein is a likely target for the anti-proliferative effects of the cholecystokinin (CCK) receptor antagonists D,L-4-benzamido-N,N-dipropylglutaramic acid (proglumide) and N-4-chlorobenzoyl-L-tryptophan (benzotript) on colorectal carcinoma cell lines [Baldwin, G.S., 1994. Antiproliferative gastrin/cholecystokinin receptor antagonists target the 78-kDa gastrin-binding protein. Proc. Natl. Acad. Sci. USA 91, 7593-7597.]. Definition of the physiological role of the gastrin-binding protein has been hampered by the very low affinity of benzotript for the gastrin-binding protein. Benzotript analogues were therefore tested for their ability to inhibit the binding of iodinated gastrin to the gastrin-binding protein. The affinity of the most potent analogue (the D-isomer of benzotript, CR 665) was similar to the value reported previously for the L-isomer. In order to isolate more potent binding inhibitors, several selective CCK receptor antagonists were also tested as inhibitors of the binding of gastrin to the gastrin-binding protein. The affinity of the most potent binding inhibitor PD 149164 (benzenebutanoic acid, 4-fluoro-!b/-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo-[3.3 .1. 1(3,7)]dec-2-yloxy)carbonyl]amino]propyl]amino]-, [R-(R*,S*)]-) was approximately 10-fold higher than the L-isomer of benzotript. PD 149164 may serve as the lead compound for the future development of more potent and selective gastrin-binding protein inhibitors.
 ...
PMID:Affinity of cholecystokinin receptor antagonists for the gastrin-binding protein. 1065 41

This review aims to report the major control mechanisms of protein and peptides digestion of special interest in human patients. Regarding protein assimilation its digestive process begins at the stomach with some not so indispensable actions comparatively to those of duodenal/jejunal lumen. However even the intestine processes are partially under gastric secretion control. Proteolytic enzyme activities are related to protein structure and amino acid constituents, tertiary and quartenary structures need HCl denaturation prior to enzymatic hydrolysis. Thereafter the exopeptidases are guided by either NH2 (aminopeptidases) or COOH (carboxypeptidases) terminals of the molecule while endopeptidases are oriented by the specific amino acids constituents of the peptide. Both dietary and luminal secreted proteins and polypeptides undergo to either limited or complete proteolysis resulting basic or neutral free-amino acids (40%) or dioctapeptides. The brush border peptidases continue to degrade oligopeptide to di-tripeptides and neutral free-amino acids. Some peptides are uptaked by the enterocytes whose cytosolic peptidases complete the hydrolysis. Hence the digestive products flowing in the portal vein are mainly free-amino acids from either luminal or cytosolic hydrolysis and some di-tripeptides intactly absorbed. Both mechanical and chemical processes of digestion are under neural (vagal), neuroendocrinal (acetilcholine), endocrinal (gastrin, secretin and cholecystokinin) or paracrinal (histamine) controls. The gastric phase (hydrochloric acid and pepsinogen secretions) is activated by gastrin, histamine and acetilcholine which respond to both dietary-amino acids (tryptophan and phenylalanine) and mechanic distention of stomach. The pancreatic secretion is stimulated by either cephalic or gastric phases and has influence on the intestinal phase of digestion. The intestinal types of cells S and I release secretin and cholecystokinin respectively in response of acid quimo (cells S) or amino acids and peptides (cells I) in the lumen. Secretin stimulates the releasing of water, bicarbonate and enteropeptidases whereas cholecystokinin acts on pancreatic enzymes.
 ...
PMID:[Mechanism of action and control in the digestion of proteins and peptides in humans]. 1075 1


<< Previous 1 2 3 4 5 Next >>