UNIPROT:P01350 - FACTA Search

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

tRNAPheE.coli was modified at accessible guanosine, cytidine, and adenosine residues using the chemical modification method described by Peattie and Gilbert [Proc. Natl Acad. Sci. USA, 77, 4679-4689 (1980)]. Modification characteristics of the tRNA in the free state, in the ternary complex with elongation factor EF-Tu and GTP and in the ribosomal A and P sites were compared. A special procedure was devised to monitor, exclusively, tRNA molecules in the aminoacylated state. In the free tRNA, the most reactive bases are confined to the A73-C-C-A sequence of the aminoacyl stem, the anticodon loop, the D-loop and the extra loop and the results correlate well with the three-dimensional structure of tRNAPheyeast determined by X-ray studies. The pattern of reactivity was not affected either by charging the tRNA with phenylalanine or by labelling the 3' terminus with pCp. In the ternary complex, with elongation factor EF-Tu and GTP, changes in modification were observed at two sites, A73-C-C-A at the 3' terminus and C-13 and C-17 in the D-loop region, which are about 6 nm apart; no difference was observed in the anticodon loop. tRNAPhe bound at the ribosomal A or P sites exhibited similar, but not identical, modification patterns. Whereas nucleotides C-74 and C-75 were strongly protected at both sites, the adjacent A-73 showed an enhanced reactivity in the A site. The anticodon region G34-A-A-ms2.6(1)A was also strongly protected at both sites. In addition, nucleotide A-21 was protected during A-site, but not P-site, binding.
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PMID:Comparison of Escherichia coli tRNAPhe in the free state, in the ternary complex and in the ribosomal A and P sites by chemical probing. 618 69

Rho, a member of the Ras superfamily of GTP-binding proteins, regulates actin polymerization resulting in the formation of stress fibers and the assembly of focal adhesions. In Swiss 3T3 cells, heterotrimeric G protein-coupled receptors for lysophosphatidic acid and gastrin releasing peptide stimulate Rho-dependent stress fiber and focal adhesion formation. The specific heterotrimeric G protein subunits mediating Rho-dependent stress fiber and focal adhesion formation have not been defined previously. We have expressed GTPase-deficient, constitutively activated G protein alpha subunits and mixtures of beta and gamma subunits in Swiss 3T3 cells. Measurement of actin polymerization and focal adhesion formation indicated that GTPase-deficient alpha 12 and alpha 13, but not the activated forms of alpha 12 or alpha q stimulated stress fiber and focal adhesion assembly. Combinations of beta and gamma subunits were unable to stimulate stress fiber or focal adhesion formation. G alpha 12- and alpha 13-mediated stress fiber and focal adhesion assembly was inhibited by botulinum C3 exoenzyme, which ADP-ribosylates and inactivates Rho, indicating that alpha 12 and alpha 13, but not other G protein alpha subunits or beta gamma complexes, regulate Rho-dependent responses. The results define the integration of G12 and G13 with the regulation of the actin cytoskeleton.
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PMID:G alpha 12 and G alpha 13 stimulate Rho-dependent stress fiber formation and focal adhesion assembly. 755 69

An intraperitoneal (i.p.) injection of pentagastrin (250 micrograms/kg, three times daily) for 1 week increased somatostatin like-immunoreactivity (SSLI) content in the pancreas and the number of somatostatin (SS) receptors in pancreatic acinar membranes without influencing their apparent affinity as compared with control animals. No significant differences were seen in basal or forskolin (FK)-stimulated adenylate cyclase (AC) enzyme activities in the control and pentagastrin treated rats. In spite of the increase in the number of SS receptors, SS caused a significantly lower inhibition in AC activity in these membranes. This finding is related to the fact that the stable GTP analogue, 5'-guanylylimidodiphosphate (Gpp[NH]p) was a much less potent inhibitor of binding in the pancreatic acinar cell membranes from pentagastrin-treated animals than in those from controls. In addition the ability of Gpp(NH)p to inhibit FK-stimulated AC activity was also decreased in pancreatic acinar cell membranes from pentagastrin-treated rats. Pretreatment with proglumide, (20 mg/kg i.p.) a gastrin/cholecystokinin (CCK) receptor antagonist, prevented the pentagastrin-induced changes in SS level and binding as well as the inhibitory effect of SS on AC activity in pancreatic acinar cell membranes. Proglumide alone had no observable effect on the somatostatinergic system. These data suggest a SS receptor/G protein uncoupling as a result of binding of pentagastrin to gastrin receptors present in pancreatic acinar cell membranes.
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PMID:The effect of pentagastrin on the somatostatin receptor/effector system in rat pancreatic acinar membranes. 771 80

Specific receptors for bombesin/gastrin releasing peptide (GRP) on the androgen-independent human prostate cancer cell lines PC-3 and DU-145 were characterized. No specific binding of 125I-[Tyr4]-bombesin to the androgen-dependent human prostate cancer cell line LNCaP was detectable. The binding of 125I-[Tyr4]-bombesin to PC-3 and DU-145 cells was found to be time- and temperature-dependent, saturable, and reversible. Scatchard analysis revealed a single class of binding sites with high affinity (Kd 9.8 x 10(-11) M for PC-3, and 9.1 x 10(-11) M for DU-145 cells at 25 degrees C) and with a binding capacity of 44,000 binding sites/cell and 19,000 binding sites/cell, respectively. Bound 125I-[Tyr4]-bombesin was rapidly internalized by PC-3 cells. The nonhydrolyzable GTP analog GTP-gamma-S caused a dose-dependent inhibition of 125I-[Tyr4]-bombesin binding to PC-3 and DU-145 cells, indicating that a G-protein (guanine nucleotide-binding protein) couples the bombesin receptor to intracellular effector systems. Bombesin and GRP(14-27) inhibited the binding of 125I-[Tyr4]-bombesin to both cell lines in a dose-dependent manner with inhibition constants (Ki) of 0.5 nM and 0.4 nM, respectively. Both cell lines express the bombesin/GRP preferring bombesin receptor subtype, since, in displacement studies, neuromedin B was more than 200 times less potent than bombesin and GRP(14-27) in inhibiting the binding of 125I-[Tyr4]-bombesin. Two synthetic bombesin/GRP antagonists, RC-3095 and RC-3110, powerfully inhibited the specific binding of 125I-[Tyr4]-bombesin with Ki 0.92 nM and 0.26 nM on PC-3 cells, and 3.3 nM and 0.89 nM on DU-145 cells, respectively. These findings indicate that the PC-3 and DU-145 human prostate cancer cell lines possess specific high-affinity receptors for bombesin/GRP, and are suitable models for the evaluation of the antineoplastic activity of new bombesin/GRP antagonists in the treatment of androgen-independent prostate cancer.
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PMID:Characterization of high-affinity receptors for bombesin/gastrin releasing peptide on the human prostate cancer cell lines PC-3 and DU-145: internalization of receptor bound 125I-(Tyr4) bombesin by tumor cells. 802 9

In the course of our study concerning gastrin and cholecystokinin (CCK) receptors, we synthesized and characterized a labelled gastrin ligand, [125I]BH[Leu15]gastrin-(5-17) (3-(3-[125I]iodo-4-hydroxyphenyl)propionyl[Leu15]gastrin-(5-17)). On isolated canine fundic mucosal cells and human Jurkat lymphoblastic cell line, known to express CCKB/gastrin receptors, the binding experiments performed indicate that [125I]BH[Leu15]gastrin-(5-17) provides a convenient biologically active ligand for cholecystokinin/gastrin receptor studies. We showed in this study that, on guinea-pig brain membranes known to possess CCKB and CCKA receptors, [125I]BH[Leu15]gastrin-(5-17) binds to a single class of high-affinity binding sites in a saturable and specific manner. [125I]BH[Leu15]gastrin-(5-17) interacts with guinea-pig brain membranes with a maximal binding capacity that is about three-fold lower than that of [125I]BHCCK8 (CCK8, the C-terminal octapeptide of cholecystokinin). The apparent affinities of CCK analogues and selective CCK receptor antagonists L-365,260 and MK-329 for the sites labelled by both probes were in accordance with a CCKB-like profile. Association-dissociation kinetics of [125I]BH[Leu15]gastrin-(5-17) and [125I]BHCCK8 were performed and compared. They showed that [125I]BHCCK8 equilibrated more slowly than [125I]BH[Leu15]gastrin-(5-17). The effects of pH, monovalent and divalent cations on binding of both probes were investigated. The results obtained did not indicate strong differences between [125I]BH[Leu15]gastrin-(5-17) and [125I]BHCCK8 binding. Binding experiments in the presence of stable analogues of GTP showed a different behavior between [125I]BH[Leu15]gastrin-(5-17) and [125I]BHCCK8. GTP gamma S strongly decreased [125I]BH[Leu15]gastrin-(5-17) binding whereas it weakly affected [125I]BHCCK8 binding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gastrin13 and the C-terminal octapeptide of cholecystokinin are differently coupled to G-proteins in guinea-pig brain membranes. 808 68

The cholecystokinin (CCK)-B receptor cloned from human brain was characterized as a gastrin receptor by using heterologous expression systems of COS-7 cells and Xenopus oocytes. 125I-gastrin binding to human CCK-B receptor expressed in COS-7 was time-dependent, saturable and also specific, as well as 125-I-CCK-8. The binding of 125I-gastrin was inhibited by CCK-8 about 10-fold more potently than by gastrin. The rank order of potency of several antagonists to 125I-gastrin binding was YM022 > CI-988 > L-365,260 > L-364,718. Addition of GTP gamma S, a nonhydrolysable analog of GTP, dose-dependently inhibited 125I-gastrin binding, and lowered the gastrin binding affinity, Gastrin (10(-9)-10(-7) M) also evoked a Ca(2+)-dependent Cl- current in Xenopus oocytes expressing CCK-B receptors. These results suggest that the pharmacological profile of the cloned human CCK-B receptor using 125I-gastrin is closely parallel to that reported in gastric mucosa, and that the receptor transduces cellular signals of gastrin as well as those of CCK-8.
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PMID:Characterization of cloned human cholecystokinin-B receptor as a gastrin receptor. 818 42

We found that GH3 cells, a rat anterior pituitary tumor cell line, expressed a single class of high-affinity binding sites for radiolabeled cholecystokinin octapeptide (CCK-8) with a Kd of 48 pM. The binding sites had high affinity for CCK-8, CCK-4, gastrin I, and L-365,260 (CCK-B antagonist), and had low affinity for devazepide (CCK-A antagonist), indicating that the binding sites are CCK-B receptors. GTP and its stable analogues inhibited radiolabeled CCK-8 binding to GH3 cell membranes, suggesting a coupling of CCK-B receptors to a G-protein.
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PMID:GH3 cells, an anterior pituitary cell line, express CCK-B receptors. 833 61

The full peptide antagonist of the pancreatic cholecystokinin (CCK) receptor, JMV 179, [Boc-Tyr(SO3H)-Ahx-Gly-dTrp-Ahx-Asp phenylethyl ester, where Tyr(SO3H) = sulfated tyrosine, Ahx = 6-aminohexanoic acid] was modified at its N-terminus by incorporation of p-hydroxyphenyl propionate (Bolton-Hunter reagent, BH) and was subsequently radioiodinated. After HPLC purification, 125I-BH-JMV-179, a CCK antagonist radioligand of high specific activity (2000 Ci/mmol) was obtained. 125I-BH-JMV-179 bound to a single population of sites on rat pancreatic plasma membranes, (Kd = 3.9 nM, Bmax = 40 pmol/mg protein). Binding was dependent on time, temperature, and protein concentration, and was fully reversible. JMV 179 radioligand detected four times as many sites as an agonist radioligand [C. Hadjiivanova, M. Dufresne, S. Poirot, P. Sozzani, N. Vaysse, L. Moroder and D. Fourmy (1992) Eur. J. Biochem. 204, 273-279]. Agonists and antagonists of the A- and B-subtype CCK/gastrin receptors inhibited 125I-BH-JMV-179 binding with an order of potency compatible with the A-subtype CCK receptor pharmacology. Moreover, the sulfate group on the tyrosine residue of the CCK peptides appeared to be of much less importance for antagonist affinity than for agonist affinity. Inhibition of 125I-BH-JMV-179 binding by agonists (except JMV 180), demonstrated the presence of two affinity classes of binding sites. The population of sites having an apparent high affinity for CCK represented 30 pmol/mg protein and threefold the number of high-affinity sites previously identified by an agonist radioligand. In presence of non-hydrolyzable GTP, all the sites bound CCK agonists with a low affinity. Moreover, saturation analysis of JMV 179 radioligand binding in the presence of CCK indicated that CCK interacted competitively with all JMV 179 sites and demonstrated binding of JMV 179 radioligand to two distinct affinity classes of sites. In the presence of GTP[S] a single affinity class of sites for JMV 179 radioligand was found as in the control experiments without CCK. This study, with the first CCK peptide antagonist radioligand, demonstrates that CCK receptors exist in two interconvertible affinity states regulated by guanine-nucleotide-binding regulatory protein(s) in rat pancreatic plasma membranes. JMV 179 radioligand does not induce receptor coupling but distinguishes the two affinity states of the CCK receptors. JMV 179 reveals the existence of populations of high-affinity and low-affinity sites for CCK which had not previously been detected by agonist radioligand binding, thus suggesting heterogeneity of CCK receptor sites in membranes.
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PMID:Study of the states and populations of the rat pancreatic cholecystokinin receptor using the full peptide antagonist JMV 179. 844 90

The specific binding characteristics of the novel cholecystokinin (CCK)B/gastrin receptor-selective peptoid antagonist radioligand [3H]PD 140376 were investigated using membrane homogenates prepared from guinea pig cerebral cerebral cortex and gastric fundic mucosa. [3H]PD 140376 (0.01-10 nM) bound to both cerebral cortex and gastric gland homogenates with comparable high affinity (Kd, 0.1-0.2 nM) and to an apparent single population of sites with Bmax values of 119 and 296 fmol/mg of protein, respectively. The level of specific binding, defined as that displaced by unlabeled CCK sulfated octapeptide, was routinely between 60 and 70% in the cortex and between 50 and 60% in the fundic mucosa. Pharmacological characterization of the [3H]PD 140376-labeled binding sites with a series of agonist and antagonist ligands selective for each of the CCK receptor subtypes demonstrated, in both preparations, an affinity profile consistent with that of the CCKB/gastrin receptor. However, Hill slopes for the competition curves for the unlabeled agonist ligands against specific [3H]PD 140376 binding were significantly less than unity, whereas those for the antagonist ligands, including unlabeled PD 140376, were close to unity. The affinity and Hill slope for PD 140376 and the related CCKB/gastrin antagonist CI-988 were unaffected by the presence of the nonhydrolyzable GTP analogue guanylyl-5'-imidodiphosphate. In contrast, guanylyl-5'-imidodiphosphate caused a characteristic decrease in affinity and an increase in the Hill slopes towards unity for the agonist ligands CCK sulfated octapeptide and pentagastrin. The binding characteristics of unlabeled PD 140376 were also unaffected by the presence of the monovalent cation sodium. In conclusion, the present study has demonstrated that [3H]PD 140376 is the most potent and selective antagonist radioligand yet described for the characterization of CCKB/gastrin receptors in the central and peripheral nervous systems.
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PMID:[3H]PD 140376: a novel and highly selective antagonist radioligand for the cholecystokininB/gastrin receptor in guinea pig cerebral cortex and gastric mucosa. 847 32

We have shown that gastrin and cholecystokinin octapeptide (CCK-8) are differently coupled to G protein (GTP-binding protein) through type B cholecystokinin receptors in guinea-pig brain membranes and Jurkat cells. Indeed, the gastrin-13 binding affinity is strongly reduced by stable guanyl nucleotides, whereas CCK-8 binding is only slightly affected. In order to determine the structural requirements regulating such coupling, we have synthesized several gastrin and cholecystokinin fragments (sulphated or unsulphated) elongated at the N-terminus of the common C-terminal tetrapeptide. We investigated their interaction with CCKB receptors in guinea pig brain membranes and Jurkat cells and their involvement in the G protein coupling. Their apparent binding affinities to CCKB receptors were measured by inhibition of [125I]Bolton Hunter-CCK-8 (3-[125I]iodo-4-hydroxyphenyl)propionyl-CCK-8) binding in the presence or absence of GTP gamma S (guanosine 5'-O-(3-thio)triphosphate) or aluminum tetrafluoride (AlF4-). Activation of the G proteins by GTP gamma S or AlF4- led to a decrease in binding affinity for the gastrin related peptides, the common CCK-gastrin C-terminal forms, the cholecystokinin hexapeptide and the unsulphated cholecystokinin heptapeptide. Sulphated CCK-7, CCK-8, and cionin apparent binding affinities were not affected. These finding indicated that the sulphated tyrosine in position 7 in CCK (as counted from the C-terminus), provides the cholecystokinin selectivity for the CCKB receptor compared to gastrin. The results are discussed with the aim to better clarify the physiological relevance of gastrin and cholecystokinin toward CCKB receptors and their related intracellular events.
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PMID:Cholecystokinin and gastrin are not equally sensitive to GTP gamma S at CCKB receptors: importance of the sulphated tyrosine. 857 34

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