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

Cholecystokinin (CCK) binding to its receptors on guinea pig gastric chief cell membranes was characterized with 125I-COOH terminal octapeptide of CCK (125I-CCK8). Specific binding of 125I-CCK8 to chief cell membranes was maximal at pH 6.0 and 30 degrees C after 180 min of incubation and reversible upon the addition of 10(-7) M unlabeled CCK8. CCK analogs such as CCK8, gastrin-I, and COOH-terminal tetrapeptide of CCK (CCK4) competitively inhibited the labeled CCK8 binding with the half maximal inhibitory concentration of 10(-10) M, 3 X 10(-7) M and 10(-6) M, respectively. Furthermore, guanine nucleotide analogs such as GTP gamma S and Gpp(NH)p also inhibited the labeled CCK8 binding to chief cell membranes. Scatchard analysis of the binding data at pH 6.0 revealed two orders of the binding sites and GTP gamma S decreased the binding by converting two binding sites of the receptors to only one site of lower affinity. These results suggest that there are specific receptors for CCK, which are coupled to a guanine nucleotide regulatory protein on guiea pig gastric chief cell membranes.
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PMID:[Cholecystokinin receptors on guinea pig gastric chief cell membranes]. 212 47

Recent studies have demonstrated the presence of both CCKA and CCKB receptors on dog and guinea pig pancreas. Although CCKA receptors are implicated in enzymatic secretion, biological effects of CCKB receptors are still unknown. We have previously found that a rat acinar pancreatic cell line (AR4-2J) possesses both receptor subtypes. In this work we report the ability of various CCK/gastrin agonists and antagonists to bind with these receptors. We found that gastrin, pentagastrin and Gastrin/CCK4 induce ornithine decarboxylase activity, an early event involved in cell proliferation, as well as 3H-thymidine incorporation. Furthermore, these effects occur at doses at which these peptides interact only with the CCKB receptor subtype. In view of these data we propose that modulation of AR4-2J cell growth by gastrin agonists specifically involve occupation of the CCKB receptor.
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PMID:Gastrin modulates growth of a rat acinar pancreatic cell line: receptor analysis and signal transduction. 226 50

For inhibition of binding of 125I-Bolton-Hunter-labeled cholecystokinin octapeptide (125I-BH-CCK-8) to guinea pig pancreatic acini, the potencies for agonists were CCK-8 greater than desulfated [des(SO3)] CCK-8 greater than gastrin-17-I greater than pentagastrin greater than CCK-4 and for the antagonists L 364718 greater than proglumide analogue 10 greater than CBZ-CCK-(27-32)-NH2. For all non-sulfated agonists, the curves were biphasic with 20% of the tracer bound to sites with high affinity for these agonists with the following relative potencies: gastrin-17-I greater than pentagastrin greater than des(SO3)CCK-8 much greater than CCK-4; whereas 80% was bound to low-affinity sites with the following potencies: des(SO3)CCK-8 greater than gastrin-17-I = pentagastrin much greater than CCK-4. For L 364718 and proglumide analogue 10, 80% of 125I-BH-CCK-8 was bound to sites with high affinity for these antagonists and 20% to sites with low affinity. Analysis of the dose-inhibition curve for CCK-8 demonstrated two binding sites; however, comparison with the analysis in the presence of 0.1 microM gastrin-17-I suggested three binding sites. The gastrin-17-I dose-inhibition curve was significantly better fit by a three-site model than by a two-site model. The affinities of the various agonists and antagonists for the three sites were compared with their abilities to inhibit binding of 125I-gastrin-I and either stimulate or inhibit CCK-8-stimulated amylase release. These results demonstrate that 125I-BH-CCK-8 binds to three classes of receptors, not two as reported previously. Two classes are CCK-preferring, bind 83% of 125I-BH-CCK-8 at tracer concentrations, and comprise high- and low-affinity CCK-preferring sites that can be distinguished by all agonists but have equally high affinity for L 364718 and proglumide 10. A third class binds 17% of the tracer, cannot be differentiated from high-affinity CCK-preferring receptors by CCK-8, and has low affinities for L 364718 and proglumide 10. Future studies relating binding of 125I-BH-CCK-8 to biological activity or characterization of the CCK receptor by using radiolabeled agonists should consider CCK interaction with three receptors, not two as was done in the past.
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PMID:Pancreatic receptors for cholecystokinin: evidence for three receptor classes. 230 86

In dispersed gastric chief cells from guinea-pig stomach, binding of iodinated cholecystokinin octapeptide (125I-CCK-8) was relatively slow, temperature-dependent, to a single class of binding sites and inhibited by various gastrin- and CCK-related agonists and receptor antagonists. Binding of iodinated gastrin-I (125I-gastrin-I) was moderately rapid, temperature-dependent, to a single class of binding sites, and inhibited by various gastrin and CCK-related agonists and receptor antagonists. Gastrin-I as well as C-terminal fragments of CCK containing from eight amino acids (CCK-8) to four amino acids (CCK-4) stimulated pepsinogen secretion and inhibited binding of 125I-CCK-8 and 125I-gastrin-I. In addition, each of five different receptor antagonists inhibited binding of 125I-CCK-8 and 125I-gastrin-I and inhibited pepsinogen secretion stimulated by CCK-8 or gastrin-I. With each of eight different agonists and with each of five different antagonists the value of IC50 for inhibition of binding of 125I-CCK-8 was not significantly different from the value of IC50 for inhibition of binding of 125I-gastrin-I, indicating that in gastric chief cells the sites to which 125I-CCK-8 binds are the same sites to which 125I-gastrin-I binds. With the agonists as well as with the antagonists, however, there was no consistent relationship between the ability of a particular agent to inhibit binding and its ability to modify pepsinogen secretion, indicating that in gastric chief cells the sites that bind 125I-CCK-8 and 125I-gastrin-I are not the receptors that mediate stimulation of pepsinogen secretion by CCK-8 or by gastrin-I.
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PMID:Binding of 125I-CCK-8 and 125I-gastrin-I to dispersed chief cells from guinea-pig stomach. 232 95

Cholecystokinin octapeptide (CCK-8) stimulated adrenocorticotropin hormone (ACTH) release from both rat anterior pituitary cells in culture and a tumor cell line of the mouse anterior pituitary (AtT-20/D16-16). The stimulation of ACTH release was dependent on the time of exposure to CCK-8 and the concentration of this peptide applied to anterior pituitary cells. Cerulein evoked ACTH release whereas human gastrin 1, CCK-4 and desulfated CCK-8 only produced minimal affects on ACTH release at concentrations of 10(-4) M. In contrast, these latter three peptides were as effective as CCK-8 in inducing the secretion of amylase from pancreatic acinar cells. Antagonists of CCK-8 receptors in the pancreas such as proglumide, benzotript and dibutyryl cyclic GMP did not affect the ACTH release response to CCK-8. The CCK-8 stimulation of ACTH release was calcium-dependent and blocked by glucocorticoid pretreatment. The mechanisms by which CCK-8 evoked ACTH release appears distinct from that of other ACTH secretagogues such as corticotropin releasing factor and vasopressin. The data suggest that CCK-8 is a corticotropin releasing factor-like agent acting through a putative novel receptor subtype in the anterior pituitary.
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PMID:Cholecystokinin-8 stimulates adrenocorticotropin release from anterior pituitary cells. 241 42

Recent studies have demonstrated gastrin receptors in some pancreatic tumors and that gastrin is a potent stimulant of pancreatic Na+-H+ exchange. In the present study we used 125I-labeled gastrin (125I-gastrin) to characterize gastrin receptors on guinea pig pancreatic acini. Binding of 125I-gastrin was temperature dependent, saturable, and specific for gastrin-related peptides. Analysis demonstrated a single class of receptors with high affinity for gastrin (Kd = 1.5 nM) and a binding capacity of 1 fmol/mg protein. Binding of 125I-gastrin was inhibited with the following relative potencies (Kd): cholecystokinin octapeptide (CCK-8) (0.35 nM) greater than gastrin-17-I = gastrin-34-I (1.5 nM) greater than pentagastrin (7 nM) greater than desulfated [des(SO3)]CCK-8 (28 nM) greater than CCK-4 (508 nM) and by the receptor antagonists CBZ-CCK-27-32-NH2 (3.5 microM) greater than proglumide analogue 10 (30 microM) greater than asperlicin (265 microM) greater than Bt2-guanosine 3',5'-cyclic monophosphate (828 micron). In contrast, for both stimulation of enzyme secretion and inhibition of binding of 125I-CCK-8 the relative potencies were CCK-8 much greater than des(SO3)CCK-8 greater than gastrin-17-I = gastrin-34-I greater than pentagastrin greater than CCK-4. For each receptor antagonist the dose-inhibition curve for gastrin-stimulated amylase release was superimpossible with that for CCK-8-stimulated amylase release. Gastrin-17-I at concentrations less than 0.1 microM did not potentiate carbachol or vasoactive intestinal peptide-stimulated amylase secretion and did not affect basal or stimulated adenosine 3',5'-cyclic monophosphate or 45Ca outflux.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of gastrin receptors on guinea pig pancreatic acini. 244 88

We describe here the properties of tert-butyloxycarbonyl-Trp-Leu-Asp-Phe-NHNH2 (A-57696), a C-terminal hydrazide analogue of tert-butyloxycarbonyl-CCK4 (Boc-Trp-Met-Asp-Phe-NH2), at four cholecystokinin (CCK) receptor-bearing tissues, the guinea pig pancreas and gall bladder (Type A), guinea pig cortex (Type B), and NCI-H345 cells, a human small cell lung cancer cell line that expresses CCK-B/gastrin receptors. Using 125I-Bolton-Hunter-cholecystokinin octapeptide (26-33) (125I-Bolton-Hunter-CCK8) as the radioligand, A-57696 was found to be selective for cortical CCK-B receptors (IC50 = 25 nM), compared with pancreatic CCK-A receptors (IC50 = 15 microM). A-57696 behaved as a competitive antagonist in reversing CCK8-stimulated pancreatic amylase secretion and phosphoinositide breakdown. By Schild analysis, its Kd was determined to be 4.7 and 6.8 microM in amylase and phosphoinositide assays, respectively. A-57696 (100 microM) did not elicit gall bladder contraction, and it inhibited contractions induced by CCK8. The Kd of A-57696 at gall bladder CCK-A receptors was 19 microM. In contrast, A-57696 behaved as a partial agonist (80% of maximal CCK8 response) in stimulating calcium mobilization at CCK-B/gastrin receptors on NCI-H345 cells. A-57696 and CCK8 inhibited each other in calcium mobilization experiments utilizing the fluorescent dye Indo-1. Stimulatory actions of CCK8 and A-57696 were reversed by the CCK-B-selective (R)-L-365,260 (100 nM), whereas at the same concentration, the CCK-A-selective (S)-L-365,260 was ineffective. Binding studies using 125I-Bolton-Hunter-CCK8 and 125I-gastrin indicated that binding sites labeled by these two ligands displayed similar affinities for CCK8, desulfated CCK8, gastrin, A-57696, and both enantiomers of L-365,260. A-57696 represents a new class of CCK-A peptide antagonist at guinea pig pancreas a new class of CCK-A peptide antagonist at guinea pig pancreas and gall bladder. Its contrasting functional activities at guinea pig CCK-A and CCK-B/gastrin receptors in a human tumor cell demonstrate that, in addition to the previously described differences in binding specificity for selective agonists and antagonists, CCK-A receptors and CCK-B/gastrin receptors have different requirements for activation.
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PMID:Distinct requirements for activation at CCK-A and CCK-B/gastrin receptors: studies with a C-terminal hydrazide analogue of cholecystokinin tetrapeptide (30-33). 260 85

Recent studies have demonstrated that cholecystokinin (CCK) receptors are heterologous in peripheral tissues and in the central nervous system and that CCK-gastrin (CCK-G) peptides are potent trophic factors for the gastrointestinal tract. In the present study we used 125I-labeled gastrin and 125I-labeled CCK to demonstrate the heterogeneity of CCK receptors on a rat pancreatic acinar cell line (AR4-2J) and analyze the role of these receptors in increasing the activity of ornithine decarboxylase. Pharmacological analysis of radioligand binding fit well with the presence of two different receptors: 1) a CCK-selective receptor having the characteristics of the CCK receptor present on normal pancreatic cells and 2) a high-affinity, low-selectivity CCK-G binding site that interacts with all CCK-G peptides sulfated and nonsulfated. CCK-G peptides stimulate ornithine decarboxylase activity with the following order of potencies (EC50): G-(2-17)-ds (0.1 nM) greater than or equal to CCK-9 (0.25 nM) greater than or equal to pentagastrin (0.4 nM) greater than CCK-4 (6 nM). This stimulation was not inhibited by CCK antagonist (asperlicin) at a concentration range that blocks the CCK receptor but does not compete with 125I-labeled gastrin binding to the CCK-G receptor. These results, obtained with CCK-G agonists and antagonists, demonstrate that ornithine decarboxylase stimulation in these cells is mediated via the CCK-G receptor.
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PMID:Cholecystokinin and gastrin peptides stimulate ODC activity in a rat pancreatic cell line. 271 9

In isolated guinea pig gastric chief cells, gastrin-I and cholecystokinin-hexapeptide (CCK-4) stimulated pepsinogen release. However, the efficacies of these two peptide were 51% of that observed with CCK-octapeptide (CCK8). CR1409 and L-364718, both of which are new CCK receptor antagonists in pancreatic acinar cells, also inhibited 10(-8) M CCK8-stimulated pepsinogen release with a half-maximal inhibitory concentration (IC50) observed at 3 x 10(-9) M, respectively. The dose response curve to CCK8 for pepsinogen release shifted to the right in the presence of CR1409 or L-364718. The IC50 of these two antagonists for the CCK8-stimulated increase in cytosolic Ca2+ concentration monitored by Fura-2 were equal to those for CCK8-stimulated pepsinogen release. By contrast, the IC50 of dibutyryl cyclic GMP, a well-known CCK receptor antagonist, for CCK8-stimulated pepsinogen release was less than that for CCK8-stimulated increase in cytosolic Ca2+ concentration. Results suggested that CCK receptors in gastric chief cells are unique and may be different from CCK receptors in other tissues previously reported.
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PMID:[Characterization of cholecystokinin receptors in gastric chief cells--effect of CCK analogs and CCK receptor antagonists on chief cells]. 281 Aug 48

Caerulein, gastrin, and C-terminal fragments of cholecystokinin (CCK) varying in length from eight (CCK-8) to four (CCK-4) amino acids stimulate pepsinogen secretion from dispersed chief cells prepared from guinea pig stomach. C-terminal fragments of CCK containing fewer than four amino acids, even when tested at concentrations as high as 3 mM, do not stimulate pepsinogen secretion. The efficacies of gastrin and the various CCK-related peptides, coupled with the pattern of action of CCK receptor antagonists, indicate that chief cells from guinea pig stomach possess two functionally distinct classes of receptors, C-receptors and G-receptors. The C-receptors can be occupied by caerulein, CCK-8, CCK-7, des(SO3)CCK-8, or des(SO3)CCK-7, and occupation of C-receptors causes full stimulation of pepsinogen secretion. G-receptors can be occupied by gastrin I, gastrin II, CCK-6, CCK-5, or CCK-4, and occupation of G-receptors causes stimulation of pepsinogen secretion that is 60% of maximal.
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PMID:Functionally distinct receptors for cholecystokinin and gastrin on dispersed chief cells from guinea pig stomach. 283 29


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