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)

COOH-terminal fragments of cholecystokinin varying in length from 1 to 3 amino acids and their NH2-terminal butyloxycarbonyl derivatives were investigated for their ability to interact with the cholecystokinin receptor on dispersed acini from guinea pig pancreas. No fragment stimulated amylase secretion when present alone, but each of the butyloxycarbonyl derivatives and the COOH-terminal tripeptide amide inhibited the stimulation of enzyme secretion by cholecystokinin. In each case the inhibition was surmounted by increasing the concentration of cholecystokinin. Each fragment also inhibited binding of 125I-labeled cholecystokinin, with significant inhibition occurring with 30 microM butyloxycarbonyl tripeptide amide, 0.3 mM butyloxycarbonyl dipeptide amide, 10 mM butyloxycarbonyl phenylalanine amide and 3 mM tripeptide amide of cholecystokinin. In each case, there was a close correlation between the ability of the fragment to inhibit binding of 125I-labeled cholecystokinin and its ability to inhibit cholecystokinin-stimulated amylase release, cholecystokinin-stimulated 45Ca outflux and cholecystokinin-stimulated residual stimulation of amylase secretion. The inhibition of amylase secretion caused by the butyloxycarbonyl tripeptide of cholecystokinin was reversible and specific for those peptides which interact with the cholecystokinin receptor (i.e., cholecystokinin, caerulein, gastrin); it did not inhibit the actions of bombesin, carbachol, physalaemin, vasoactive intestinal peptide, secretin, PHI, ionophore A23187 or 8-bromo cyclic AMP. These results demonstrate that COOH-terminal fragments of cholecystokinin comprise a new class of cholecystokinin receptor antagonists.
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PMID:COOH-terminal fragments of cholecystokinin. A new class of cholecystokinin receptor antagonists. 618 22

Specific binding of 125I-labeled gastrin to rat gastric mucosal membranes was found to vary with serum gastrin levels. The dissociation equilibrium constants were not significantly different between receptor preparations. However, the binding capacities of the membrane preparations were directly correlated with serum gastrin levels. Fasting, feeding a liquid diet, and antrectomy significantly decreased serum gastrin and the concentrations of the gastrin receptor. Treatment of fasted and liquid-fed animals with pentagastrin prevented the decrease in receptors. Vagotomy increased both binding capacity and serum gastrin levels. These data indicate that gastrin stimulates the production of its own receptor. The upregulation of the gastrin receptor was evident if the binding capacity was expressed per milligram of protein, per microgram of DNA, or per amount of 125I-labeled choleragen bound to the same membrane preparation. This indicates that the biological response to gastrin is controlled in part by the regulation of the number of gastrin receptors present and that gastrin plays a role in this regulatory process.
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PMID:Mucosal gastrin receptor. III. Regulation by gastrin. 624 44

We used membrane preparations of rat oxyntic gland mucosa to test the binding of various gastrin analogues to the gastrin receptor. Using [125I]15-Leu G-17 as a marker, a concentration of 4 X 10(-9) M unlabeled G-17 inhibited binding 50%. The tetra-, penta-, and hexapeptides of gastrin caused similar 50% inhibitions of binding at concentrations of 1 X 10(-7) M, 3 X 10(-8) M, and 7 X 10(-9) M, respectively. The heptapeptide caused only slightly less inhibition than G-17, whereas the decapeptide was equivalent in potency. Neither the G-17 nor G-34 that had the active tetrapeptide removed caused 50% inhibition of binding. When compared to G-17, these analogues produced only a 25% inhibition of binding at concentrations of 10(-8) M. We also failed to inhibit binding more than 25% when we used an analogue that had the amide removed from the C-terminal phenylalanine. Atropine, metiamide, and mepyramine did not alter the binding of gastrin to receptor. The results of binding specificity approximate the changes in biological potency associated with these compounds. This study adds further support that the gastrin receptor in question is responsible for the physiological effects of the hormone.
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PMID:Mucosal gastrin receptor. IV. Binding specificity. 625 80

We determined the development of the oxyntic gland mucosal gastrin receptor in rats killed at various times from 5 to 60 days after birth. Rats were weaned on the 18th day after birth. Newborn animals had no detectable gastrin binding, high serum gastrin levels (800-1,200 pg/ml), low antral gastrin levels (0.5-2.0 micrograms/g tissue), or high pH of gastric contents (pH greater than 5.0) and did not respond to pentagastrin. At the time of weaning, serum gastrin dropped to 600 pg/ml and reached adult levels (300 pg/ml) on day 40. Antral gastrin increased to 7.5 micrograms/g tissue on day 20 and reached adult levels (20 micrograms/g tissue) on day 22. Specific binding of gastrin was first detected on day 20 and reached the adult level of 4 fmol/mg protein on day 60. Pentagastrin significantly stimulated acid secretion on day 20 and DNA synthesis on day 25. Prevention of weaning through day 25 decreased the magnitude but did not prevent or delay the onset of the above changes. These results indicate that 1) the absence of a gastrin response in newborn rats is due to a lack of gastrin receptors, 2) development of gastrin receptor and biological sensitivity to gastrin appear at the time of weaning, and 3) the development that occurs with weaning is enhanced but not triggered by the shift to solid food.
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PMID:Mucosal gastrin receptor. V. Development in newborn rats. 625 50

Serum and antral gastrin levels as well as specific binding of [125I]gastrin-17 to a 270-30,000 g oxyntic gland mucosa crude membrane preparation were measured in rats between 5 and 40 days of age. Rats were normally weaned at day 18, although weaning was prevented in some animals until day 25. The results of these studies confirmed our previous data showing that mucosal gastrin receptors and antral gastrin levels begin to increase at the time of normal weaning and reach adult levels within a few days. Although the shift from liquid to a solid diet enhances the response, it is not essential for it and does not trigger it. In addition, the current studies demonstrated that injection of corticosterone caused a premature increase in both gastrin receptor and antral gastrin levels. Once maturation had occurred, however, corticosterone had no further effect. Adrenalectomy delayed but did not prevent the maturational changes in gastrin receptors and antral gastrin levels. Normal serum gastrin concentrations were necessary for the number of gastrin receptors and the amount of antral gastrin to reach normal levels.
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PMID:Mucosal gastrin receptor. VI. Induction by corticosterone in newborn rats. 626 99

A series of experiments were performed to examine the long-term upregulation of the gastrin receptor and to explore the possibility of a short-term down regulation with regard to the time course of the trophic action of gastrin. Vagotomy or fasting was used to examine upregulation. Elevated serum gastrin levels observed postvagotomy are accompanied by an increase in gastrin binding capacity. Conversely, fasting caused a decline in serum gastrin and receptor levels; refeeding restored both values to normal levels. Cycloheximide was used to study the role of protein synthesis in the upregulation of gastrin receptors in vagotomized and refed rats, and it prevented the rise of gastrin binding capacity to either normal or above-normal values. This indicates that protein synthesis may play an integral part of receptor upregulation. Following the injection of gastrin-17, there was a short-term induction of downregulation. These results coupled with the maximal reduction of gastrin receptor 3 h after cycloheximide injection indicate that the gastrin receptor has a short half-life. Following the gastrin receptor interaction, the cellular response occurs at discrete periods and manifests itself as both down- and upregulation.
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PMID:Mucosal gastrin receptor. VII. Up- and downregulation. 627 53

A gastrin receptor, identified in crude membrane preparations of rat oxyntic gland mucosa, has an equilibrium dissociation constant (Kd) of approx. 4 . 10(-10)M and a binding capacity of 4 fmol/mg protein. The binding capacity was significantly lower after 2 days of fasting, parallel with a significant drop in serum gastrin levels; there was no change in Kd. In order to verify Scatchard analysis and to determine if there was a coincident alteration in the association (k+1) and dissociation (k-1) rates in the fasted rat, a kinetics study was performed. Under our conditions, there appeared to be a single set of binding sites and the binding reaction obeyed first-order dissociation, and second-order association rate kinetics. Second-order association rate kinetics were validated by demonstrating the independence of the rate constants when there were alterations in the concentrations of reactants. The average k+1 was determined to be 2 . 10(6) M-1 . s-1. The average k-1 was determined to be 1 . 10(-3) s-1. There was no significant change in the k+1 and k-1 in fed and fasted rats. Fasting decreased the number of gastrin receptors without altering the affinity of the receptor for the hormone.
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PMID:Characterization of the interaction between gastrin and its receptor in rat oxyntic gland mucosa. 628 11

The aspartic acid residue at the penultimate position is known to be essential for the hormonal activity of CCK and gastrin on gastric acid secretion. This residue was successively replaced by beta-aspartic acid, beta-alanine, and glutamic acid in the C-terminal heptapeptide of CCK 27-33. The analogues obtained were tested on rat gastric acid secretion and for recognition by gastrin receptors. The replacement by beta-aspartic or beta-alanine decreased gastric secretion and gastrin receptor recognition. In contrast, replacement by glutamic acid affected these two parameters less. The nature of the N-blocking group (Boc or Z) also influenced these activities, Boc derivatives being more potent than Z derivatives. The results were compared to those previously obtained on pancreatic secretion and on stimulation of gall bladder contraction where the modifications were found capable of differentiating between cholecystokinin, pancreozymin and gastrin activities.
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PMID:The role of the Asp-32 residue of cholecystokinin in gastric acid secretion and gastrin receptor recognition. 630 19

The gastrin receptor in rat oxyntic gland mucosa is highly regulated. This regulation has so far only been found to be directed at the total numbers of receptors present. The affinity of the receptor is not altered significantly by agents which affect receptor numbers. Homospecific regulation occurs in that gastrin upregulates its receptor over long periods of time. Upregulation, however, appears to be preceded by a brief period of downregulation. During development corticosterone triggers the synthesis, or at least the appearance of gastrin receptors. Receptor development is maintained by solid food and presumably the gastrin it releases, but the change in diet which occurs at weaning does not in itself induce development. In female rats, estrogens prevent the increase of gastrin receptor levels to those found in males. These results with the gastrin receptor emphasize the importance of studying receptor concentrations as well as hormone levels to the total understanding of an endocrine response. They also suggest that the receptors of the other gastrointestinal hormones are likely to be regulated and that this regulation will probably be important in understanding some of the diseases of the gastrointestinal tract.
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PMID:Regulation of the mucosal gastrin receptor. 630 67

Proglumide, a glutaramic acid derivative, inhibits the acid secretory effects of gastrin and is said to be a specific gastrin receptor blocking agent. In the current study we have shown that proglumide inhibits the binding of gastrin to its receptor in rat oxyntic gland mucosa and tested whether this receptor is also responsible for the trophic effect of gastrin. In the first study 400 mg/kg proglumide injected with 250 micrograms/kg pentagastrin every 8 h for 48 h totally prevented the trophic effects of pentagastrin in rat oxyntic gland mucosa. Parameters measured included DNA synthesis and DNA, RNA, and protein content. In a second study the lowest maximally effective dose of proglumide was determined to be 100 mg/kg. The trophic effect of pentagastrin was inhibited in duodenal mucosa, colonic mucosa, and pancreas as well as oxyntic gland mucosa. These data demonstrate that proglumide blocks the trophic action of exogenous gastrin and suggest that the trophic effect of gastrin is mediated by the gastrin receptor.
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PMID:Proglumide inhibition of trophic action of pentagastrin. 632 Jun 64


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