Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The nonapeptide, Phe-Asp-Asp-Tyr(SO3)-Gly-His-Met-Arg-Phe-NH2 was isolated from heads of the blowfly Calliphora vomitoria. Designated callisulfakinin I, the peptide is identical to the earlier known drosulfakinin I of Drosophila melanogaster and to neosulfakinin I of Neobellieria bullata. It belongs to the sulfakinin family, all known members of which (from flies, cockroaches and locusts) have the C-terminal heptapeptide sequence Asp-Tyr(SO3)-Gly-His-Met-Arg-Phe-NH2. The callisulfakinin gene of C. vomitoria was cloned and sequenced. In addition to callisulfakinin I, the DNA revealed a coding sequence for the putative tetradecapeptide. Gly-Gly-Glu-Glu-Gln-Phe-Asp-Asp-Tyr-Gly-His- Met-Arg-Phe-NH2, callisulfakinin II. However, this peptide was not identified in the fly head extracts. Confocal laser scanning immunocytochemical studies with antisera raised against the synthetic undecapeptide C-terminal fragment of drosulfakinin II from D. melanogaster, Asp-Gln-Phe-Asp-Asp-Tyr(SO3)- Gly-His-Met-Arg-Phe-NH2, revealed only four pairs of sulfakinin neurones in the brain of C. vomitoria and no others anywhere else in the neural, endocrine or gut tissues. In situ hybridisation studies with a digoxigenin-labelled sulfakinin gene probe (from the blowfly Lucilia cuprina) also revealed only four pairs of neurones in the brain. The perikarya of two pairs of cells are situated medially in the caudo-dorsal region, close to the roots of the ocellar nerve. The other perikarya are slightly more posterior and lateral. Although it has been suggested by several authors that the insect sulfakinins are homologous to the vertebrate peptides gastrin and cholecystokinin, such arguments (based essentially on C-terminal structural similarities) do not take account of important differences in the C-terminal tetrapeptide. His-Met-Arg-Phe-NH2 in the sulfakinins, compared with Trp-Met-Asp-Phe-NH2 in gastrin and cholecystokinin. Furthermore, whereas the sulfakinin neurons of C. vomitoria are small in number and have a very specialised location, a greater number of cells throughout the nervous system react positively to gastrin/cholecystokinin antisera. Chromatographic profiles of the present study also revealed peaks of gastrin/cholecystokinin-immunoreactive material separate from the sulfakinin peptides. This evidence suggests that the insect and vertebrate peptides may not necessarily be homologous.
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PMID:The sulfakinins of the blowfly Calliphora vomitoria. Peptide isolation, gene cloning and expression studies. 755 17

Gastrin component I is the largest hormonally active form of gastrin. In order to determine its structure, we isolated progastrin-derived peptides from normal human antral tissue. A radioimmunoassay specific for sequence 20-25 of human progastrin was developed to monitor the purifications. After four or five steps of reverse-phase chromatography, the peptides were pure and could be identified by a combination of microsequence, amino acid and mass spectral analysis as well as by a library of sequence-specific immunoassays. In addition to intact progastrin 1-80, fragments 1-71, 1-35, 6-35, 20-35, and 20-36 of progastrin were identified. Only the 71-amino-acid peptide contained at its C-terminus the alpha-amidated bioactive site (Trp-Met-Asp-Phe-NH2). This unoheptacontapeptide amide (gastrin-71) corresponds to component I and is the largest possible bioactive product of progastrin. Its structure shows that progastrin is used in its entirety for biosynthesis of active peptides. The occurrence of fragments 6-35, 20-35, and 20-36 demonstrate that antral progastrin is partially cleaved at two monobasic sites (Arg5 and Arg19) in addition to processing at the three C-terminal dibasic sites. The results show that both the N- and C-terminal parts of antral progastrin undergo extensive processing. The results also suggest that progastrin may follow two different processing pathways of which the less trafficked releases gastrin-71.
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PMID:Identification of gastrin component I as gastrin-71. The largest possible bioactive progastrin product. 805 52

The distribution of neurones immunoreactive to antisera raised against the undecapeptide C-terminal fragment of drosulfakinin II (DrmSKII), Asp-Gln-Phe-Asp-Asp-Tyr(SO3H)-Gly-His-Met-Arg-Phe-NH2, has been studied in the blowfly Calliphora vomitoria. Antisera were preabsorbed with combinations of the parent antigen, the tetrapeptide Phe-Met-Arg-Phe-NH2 and cholecystokinin, the vertebrate sulfated octapeptide (CCK-8), Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2, in order to ensure specificity for the sulfakinin peptides of C. vomitoria (the nonapeptide callisulfakinin I is identical to drosulfakinin I and callisulfakinin II differs from DrmSK II only by the presence of -Glu3-Glu4- in place of -Asp3-Asp4-). Only four pairs of sulfakinin-immunoreactive neurons have been visualised in the entire nervous system. These occur in the brain: two pairs of cells situated medially in the caudo-dorsal region close to the roots of the ocellar nerve and two other pairs at the same level but positioned more laterally. Despite the small number of sulfakinin-immunoreactive cells, there are extensive projections to many areas of neuropile in the brain and the thoracic ganglion. The pathway of the medial sulfakinin cells extends into each of the three thoracic ganglia and a metameric arrangement of sulfakinin neuronal projections is also seen in the abdominal ganglia. Neither the dorsal neural sheath of the thoracic ganglion, nor the abdominal nerves contain sulfakinin-immunoreactive material. These observations suggest that the sulfakinins of the blowfly function as neurotransmitters or neuromodulators. They do not appear to have a direct role in gut physiology, as has been shown by in vitro bioassays for the sulfakinins of orthopterans and blattodeans. In addition to the neurones that display specific sulfakinin immunoreactivity, other cells within the brain and thoracic ganglion are immunoreactive to cholecystokinin/gastrin antisera. There are, therefore, at least two types of dipteran neuropeptides with amino acid sequences that are similar to the vertebrate molecules cholecystokinin and gastrin.
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PMID:Localisation of sulfakinin neuronal pathways in the blowfly Calliphora vomitoria. 811 42

Isolated gastric glands from rabbit were used to characterize the functional cholecystokinin (CCK)-like peptide receptors that mediate pepsinogen secretion. Pepsinogen secretion was stimulated by both CCK octapeptide sulfate (CCK-8) and A-71378, a selective CCK-A-type receptor agonist, with similar mean effective doses (1.0 and 0.8 nM, respectively). Compared with CCK-8, gastrin-17 (G-17-I) showed reduced potency and only partial efficacy for stimulation of pepsinogen secretion while inhibiting the maximal CCK-8-stimulated response. The nonpeptide inhibitors, asperlicin and L-364,718, inhibited pepsinogen secretion with identical pA2 values for antagonism of both CCK and gastrin, indicating that both peptides interact with the same functional receptor. Specific binding of [3H]CCK-8 to isolated chief cell membranes was displaced fully by both CCK and gastrin, indicating full receptor occupancy by both peptides. A novel synthetic peptide analogue, pseudogastrin [(Glu)5-Ala-Tyr-Nle-Gly-Trp-Nle-Asp-Phe-NH2], was used to investigate the structural basis for the lower potency and efficacy of G-17-I. The potency of CCK and gastrin analogues for pepsinogen secretion was found to be dependent on both sulfation of a tyrosine residue and the position of the tyrosine residue relative to the COOH-terminal phenylalanine amide. The efficacy appears to be determined partially by the extended NH2-terminal sequence of G-17-I. The results of the present study are interpreted to show that pepsinogen secretion is mediated by a CCK-A-type receptor and gastrin acts at the same receptor as a partial agonist.
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PMID:Partial agonism by gastrin for a cholecystokinin receptor mediating pepsinogen secretion. 823 15

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

Five tridecapeptides have been identified from the central nervous system of the pond snail, Lymnaea stagnalis. The sequences are Pro-Xaa-Asp-Arg-Ile-Ser-Yaa-Ser-Ala-Phe-Ser-Asp-Phe. NH2, where Xaa is either Tyr or Phe and Yaa either Asn, Ser or Gly. The peptides are named lymnaDFamides to acknowledge identity with the C-terminal dipeptide of the mammalian neuropeptides, cholecystokinin (CCK) and gastrin. They were detected by an antiserum that recognizes the biologically active C-termini of cholecystokinin and gastrin. LymnaDFamide-1 (Xaa = Tyr and Yaa = Asn) had no effect on trout gallbladder, which responds equally to CCK and gastrin. We propose that the lymnaDFamides belong to an Asp-Phe-amide superfamily, which includes CCK and gastrin, and suggest that the widespread CCK/gastrin immunoreactivity in invertebrates is due to peptides belonging to such a superfamily.
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PMID:LymnaDFamides, a new family of neuropeptides from the pond snail, Lymnaea stagnalis. Clue to cholecystokinin immunoreactivity in invertebrates? 847 56

A single-strand-specific nuclease from wheat chloroplasts (ChS nuclease) was tested as a tool for RNA secondary and tertiary structure investigations, using yeast tRNA(Phe) and yeast tRNA(Asp) as models. In tRNA(Phe) the nuclease introduced main primary cleavages at positions U33, A35 and A36 in the anticodon-loop and G18 and G19 in the D-loop. In tRNA(Asp) the main primary cleavages occurred at positions U33, G34 and U35 in the anticodon-loop and the lower one at position C20:1 in the D-loop. No primary cleavages were observed within the double-stranded stems. Because ChS nuclease has (i) a low molecular weight, (ii) a wide pH range of action (5.0 to 7.5) (iii) no divalent cation requirement in the reaction mixture and (iv) can be obtained as a pure protein in rather large quantities it appeared to be a very good tool for secondary and tertiary structural studies of RNAs.
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PMID:Structural specificity of nuclease from wheat chloroplasts stroma. 864 43

In the present study we compared various CCK(B) receptor antagonists and tried to detect a difference in biological activity between the C-terminal octapeptides of cholecystokinin (CCK-8) and [Leu11]gastrin-(5-17) in isolated rabbit gastric glands. Binding experiments showed that different CCK(B)/gastrin receptor agonists bound with high affinity and that antagonists inhibited this binding in accordance with a CCK(B)/gastrin pharmacological profile. [Leu11]gastrin-(5-17), CCK-8 and cionin were found to induce [14C]aminopyrine accumulation to 25% above the basal level. Under the same experimental conditions, histamine induced a response twice as great as the response obtained with [Leu11]gastrin-(5-17) or CCK-8. [Leu11]gastrin-(5-17) (10(-7) M), CCK-8 (10(-8) M) and cionin (10(-8) M) appeared to be full agonists. CCK(B)/gastrin receptor antagonists including L-365,260 (3R-(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin++ +-3-yl)-N-(3-methylphenyl) urea), L-364,718 (3S-(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin++ +-3-yl)-1H-indole-2-carboximide) (a selective CCK(A) receptor antagonist), PD-135,158 (4([2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[[1.7.7-trimethyl-bicyclo[2. 2.1]hept-2-yl)oxy]carbonyl]amino]propyl]amino]-1-phenylethyl] amino-4-oxo-[1S-1alpha.2beta[S*(S*)]4alpha]]-butano nate N-methyl-D-glucamine) (bicyclo system 1S-endo), YM-022 ((R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1,4-++ +benzodiazepin-3-yl]-3-(3-methylphenyl)urea) and JMV-180 (Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-O-CH2-CH2-C6H5) exhibited the same profile for inhibition of [Leu11]gastrin-(5-17) or CCK-8-induced [14C]aminopyrine accumulation in rabbit gastric glands. These results suggested that [Leu11]gastrin-(5-17) and CCK-8 induced [14C]aminopyrine accumulation by the same mechanism. [Leu11]gastrin-(5-17)- or CCK-8-induced [14C]aminopyrine accumulation was inhibited by about 40% by the histamine H2 receptor blocker cimetidine. These results are consistent with there being cooperativity between [Leu11]gastrin-(5-17) (or CCK-8) and histamine in the acid secretory pathway. Similarly, the CCK(B)/gastrin receptor antagonists were tested against histamine-induced [14C]aminopyrine accumulation and surprisingly, only compound L-365,260 appeared active and even more potent than cimetidine.
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PMID:Are C-terminal octapeptide of cholecystokinin and [Leu11]gastrin-(5-17) different in stimulating acid secretion in isolated rabbit gastric glands? 875 Jul 13

Elements that confer identity to a tRNA in the cellular environment, where all aminoacyl-tRNA synthetases are competing for substrates, may be delineated by in vivo experiments using suppressor tRNAs. Here we describe the selection of active Escherichia coli tRNAAsp amber mutants and analyze their identity. Starting from a library containing randomly mutated tRNA(CUA)Asp genes, we isolated four amber suppressors presenting either lysine, alanine, or glutamine activity. Two of them, presenting mainly alanine or lysine activity, were further submitted to a second round of mutagenesis selection in order to improve their efficiency of suppression. Eleven suppressors were isolated, each containing two or three mutations. Ten presented identities of the two parental mutants, whereas one had switched from lysine to arginine identity. Analysis of the different mutants revealed (or confirmed for some nucleotides) their role as positive and/or negative determinants in AlaRS, LysRS, and ArgRS recognition. More generally, it appears that tRNAAsp presents identity characteristics closely related to those of tRNALys, as well as a structural basis for acquiring alanine or arginine identity upon moderate mutational changes; these consist of addition or suppression of the corresponding positive or negative determinants, as well as tertiary interactions. Failure to isolate aspartic acid-inserting suppressors is probably due to elimination of the important G34 identity element and its replacement by an antideterminant when changing the anticodon of the tRNAAsp to the CUA triplet.
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PMID:Selection of tRNA(Asp) amber suppressor mutants having alanine, arginine, glutamine, and lysine identity. 880 18

Multiple molecular dynamics trajectories of the solvated and neutralized 17-residue tRNA(Asp) anticodon hairpin were generated for a total of 3 ns. Explicit treatment of all long-ranged electrostatic interactions by the particle mesh Ewald algorithm, as implemented in the AMBER MD software package, effected a degree of structural stabilization not previously achieved by use of a long 16-A solvent interaction truncation scheme. The increased stability of this multiple molecular dynamics set was appropriate for an in-depth analysis of the six 500-ps-long trajectories and allowed the characterization of a number of key structural interactions. The dynamical behavior of the standard Watson-Crick base pairs, the noncanonical G30-U40 "wobble" base pair, and the psi 32-C38 pseudo-base pair is presented as well as that of two C--H... O hydrogen bonds found to contribute to the array of tertiary interactions that stabilize the seven-nucleotide native loop conformation. The least mobile residue in the loop is U33, which forms the U-turn motif and which participates in several hydrogen-bonding interactions, whereas the most mobile residue is the apical residue G34 at the wobble position, a factor undoubtedly important in its biological function. The set of multiple molecular dynamics trajectories obtained does not converge on a 500-ps time scale to a unique dynamical model but instead describes an ensemble of structural microstates accessible to the system under the present simulation protocol, which is the result of local structural heterogeneity rather than of global conformational changes.
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PMID:H-bond stability in the tRNA(Asp) anticodon hairpin: 3 ns of multiple molecular dynamics simulations. 884 34


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