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)

Competitive inhibition binding studies on membranes from the rat pancreatic AR 4-2J cell line revealed the predominance (80%) of low selectivity CCK receptors (KD of 1 nM and 4 nM for, respectively, CCK-8 and gastrin-17I (G-17I] over selective receptors (20% with a KD of 1 nM and 1 microM for, respectively, CCK-8 and G-17I). Amylase secretion was stimulated by low concentrations of CCK-8, G-17I and CCK-4. G-17I-induced amylase secretion was unaffected by 100 nM of the selective peripheral CCK-A receptor antagonist L-364,718, suggesting that amylase hypersecretion followed non-selective CCK receptor activation, a function normally assumed by selective CCK-A receptors in rat pancreatic acini. Direct ultraviolet irradiation of AR 4-2J cell membranes preloaded with 125I-BH-CCK-33 or 125I(Leu)G(2-17)I resulted in covalent cross-linking with, respectively, a 90 kDa protein and a 106 kDa protein, both distinct from the 81 kDa CCK binding species revealed in normal rat pancreatic membranes. Gpp[NH]p increased the dissociation rate of CCK-8 and G-17I from AR 4-2J cell membranes, indicating a coupling of receptors with guanyl nucleotide regulatory protein(s) G. [32P]ADP-ribosylation of AR 4-2J cell membranes allowed to detect the presence of two Gs alpha (the 50 kDa form predominating over the 45 kDa form) and one Gi alpha (41 kDa). However, Gi and Gs may not be involved in gastrin stimulation of amylase secretion, as Bordetella pertussis toxin and cholera toxin pretreatment of cells did not suppress G-17I-dependent amylase secretion.
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PMID:Functional and molecular characterization of CCK receptors in the rat pancreatic acinar cell line AR 4-2J. 170 48

Two distinct light-regulated G-proteins were found in octopus photoreceptors. Gip, a 41 kDa protein from washed microvilli, was ADP ribosylated by pertussis toxin in the presence of GDP in the dark. Light and GTP analogues were inhibitory as with transducin (Gt; G-protein in vertebrate photoreceptors). G34, a 34 kDa protein from fresh octopus retina, was ADP ribosylated by both cholera and pertussis toxin in the dark. Light inhibited labeling of the 34 kDa protein by both toxins. Unlike Gip, G34 is soluble and is very labile to heat, freezing and thawing. Prolonged incubation of octopus retina with cholera toxin and labeled NAD produced an additional radioactive band at 46 kDa. Labeling of the 46 kDa protein, Gsp, was greatly enhanced by GTP analogues, but inhibited by a GDP analogue as with Gs in hormone-sensitive adenylate cyclase. In contrast to Gip and G34, labeling of the 46 kDa protein (Gsp) was not influenced by light. The two distinct light-regulated G-proteins, Gip and G34, found in octopus photoreceptors might be involved in either phototransduction or photoadaptation. The function of Gsp is not known.
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PMID:Two distinct light regulated G-proteins in octopus photoreceptors. 210 29

In muscularis mucosae from the opossum distal colon, both tone and spontaneous contractions were highly dependent on the available oxygen. Acetylcholine and histamine caused, respectively, atropine- and pyrilamine-sensitive contractions. Norepinephrine relaxed the tissue, an effect abolished by propranolol. Under these conditions norepinephrine failed to elicit contractions and at higher concentrations again caused relaxations. The tissue gave concentration-dependent relaxations to ATP but not to ADP, AMP, or adenosine. Electrical field stimulation (20-30 Hz, 1-2 ms, 120 mA) revealed a cholinergic excitatory innervation and a nonadrenergic, noncholinergic neural inhibition. Cholecystokinin, gastrin, substance P, and vasoactive intestinal polypeptide were without effect on this tissue. In these respects, colonic muscularis mucosae differs considerably from that of other gastrointestinal viscera.
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PMID:Pharmacological characterization of opossum distal colonic muscularis mucosae in vitro. 394 17

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

The conserved glycines in the glycine-rich loop (Leu-Gly50-Thr-Gly52-Ser-Phe-Gly55-Arg-Val) of the catalytic (C) subunit of cAMP-dependent protein kinase were each mutated to Ser (G50S, G52S, and G55S). The effects of these mutations were assessed here using both steady-state and pre-steady-state kinetic methods. While G50S and G52S reduced the apparent affinity for ATP by approximately 10-fold, substitution at Gly55 had no effect on nucleotide binding. In contrast to ATP, only mutation at position 50 interfered with ADP binding. These three mutations lowered the rate of phosphoryl transfer by 7-300-fold. The combined data indicate that G50 and G52 are the most critical residues in the loop for catalysis, with replacement at position 52 being the most extreme owing to a larger decrease in the rate of phosphoryl transfer (29 vs 1.6 s-1 in contrast to 500 s-1 for wild-type C). Surprisingly, all three mutations lowered the affinity for Kemptide by approximately 10-fold, although none of the loop glycines makes direct contact with the substrate. The inability to correlate the rate constant for net product release with the dissociation constant for ADP implies that other steps may limit the decomposition of the ternary product complex. The observations that G52S (a) selectively affects ATP binding and (b) significantly lowers the rate of phosphoryl transfer without making direct contact with either the nucleotide or the peptide imply that this residue serves a structural role in the loop, most likely by positioning the backbone amide of Ser53 for contacting the gamma-phosphate of ATP. Energy-minimized models of the mutant proteins are consistent with the observed kinetic consequences of each mutation. The models predict that only mutation of Gly52 will interfere with the observed hydrogen bonding between the backbone and ATP.
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PMID:Kinetic analyses of mutations in the glycine-rich loop of cAMP-dependent protein kinase. 960 Oct 30

It has been suggested that muscularis mucosae excitation may augment gastric acid secretion, implying that this muscle should contract to secretagogues or stimulation of its motor innervation. The aim of this study was to characterize in vitro the responses of the muscularis mucosae in the rabbit gastric corpus to substances that modulate acid release and to intrinsic nerve stimulation. Muscularis mucosae from both fundic and antral ends of the corpus had identical mechanical properties, contracted to ACh, ADP, ATP, and histamine but relaxed to vasoactive intestinal polypeptide. Fundic but not antral muscularis mucosae contracted to bombesin and PGE2 and PGF2alpha, whereas adenosine, AMP, CCK, gastrin, secretin, and somatostatin were without effect on any preparation. In both regions electrical field stimulation evoked TTX-sensitive responses consisting of an atropine-resistant contraction followed by an NG-nitro-L-arginine methyl ester- and indomethacin-resistant relaxation. It is concluded from the regional variability in the pharmacological properties of the gastric muscularis mucosae that if its motor activity is linked to acid secretion this would be achieved by a neurally mediated relaxation rather than a paracrine- and/or endocrine-induced alteration in tone.
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PMID:Characteristics of the muscularis mucosae in the acid-secreting region of the rabbit stomach. 1033 12

It is common practice to coadminister proton pump inhibitors with aspirin to diminish the risk of upper gastrointestinal bleeding. This is the first study that investigated the potential impact of a proton pump inhibitor on aspirin effects on platelet aggregation. Twenty-four hypertensive subjects eligible for treatment with low-dose enteric-coated aspirin (LDECA) for primary prevention of cardiovascular disease were randomized to receive 100 mg LDECA or 100 mg LDECA plus 30 mg lansoprazole for 4 weeks. Then, participants were crossed over to the alternative regimen for another 4 weeks. Salicylic, gastrin, and pepsinogen I blood level counting were used to ensure adherence to treatment. Platelet aggregation was evaluated by light transmittance aggregometry and PFA100. The LDECA administration reduced arachidonic acid (P < 0.001), collagen (P < 0.01), and epinephrine (P < 0.001) tests. These changes paralleled an increase in collagen/epinephrine duration (P < 0.001) but not in collagen/adenosine diphosphate duration and platelet count. No significant difference was found in any of these platelets' function tests with LDECA alone versus LDECA plus lansoprazole. A significant increase in salicylic levels was observed in patients on LDECA as well as in those on LDECA plus lansoprazole, whereas gastrin and pepsinogen I levels were increased only when lansoprazole was added. These data suggest that the concomitant use of the lansoprazole at 30-mg daily does not influence the long-term effect of LDECA on platelet aggregation. Furthermore, they might imply that an interaction of LDECA with other proton pump inhibitors on platelet aggregation is unlikely.
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PMID:Do proton pump inhibitors attenuate the effect of aspirin on platelet aggregation? A randomized crossover study. 1956 78

F1 domain of F(1)F(o)-ATPase was initially believed to be strictly expressed in the mitochondrial membrane. Interestingly, recent reports have shown that the F1 complex can serve as a cell surface receptor for apparently unrelated ligands. Here we show for the first time the presence of the F(1)-ATPase at the cell surface of normal or cancerous colonic epithelial cells. Using surface plasmon resonance technology and mass spectrometry, we identified a peptide hormone product of the gastrin gene (glycine-extended gastrin (G-gly)) as a new ligand for the F(1)-ATPase. By molecular modeling, we identified the motif in the peptide sequence (E(E/D)XY), that directly interacts with the F(1)-ATPase and the amino acids in the F(1)-ATPase that bind this motif. Replacement of the Glu-9 residue by an alanine in the E(E/D)XY motif resulted in a strong decrease of G-gly binding to the F(1)-ATPase and the loss of its biological activity. In addition we demonstrated that F(1)-ATPase mediates the growth effects of the peptide. Indeed, blocking F(1)-ATPase activity decreases G-gly-induced cell growth. The mechanism likely involves ADP production by the membrane F(1)-ATPase, which is induced by G-gly. These results suggest an important contribution of cell surface F(1)-ATPase in the pro-proliferative action of this gastrointestinal peptide.
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PMID:Identification of the F1-ATPase at the cell surface of colonic epithelial cells: role in mediating cell proliferation. 2305 19