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)

Bombesin and its mammalian counterpart gastrin releasing peptide (GRP) are potent mitogens for Swiss 3T3 cells in which distinct high affinity receptors have been identified. We developed here a probe for specific ligand affinity chromatography by coupling biotin to [lys3]bombesin. The resulting biotinylated [lys3]bombesin (BLB) retained biological activity as judged by inhibition of [125I]GRP binding to intact cells and membrane preparations and stimulation of rapid Ca2+ mobilization and DNA synthesis in intact cells. Using this ligand and magnetised beads coated with streptavidin, we extracted differentially a single protein from detergent-solubilized Swiss 3T3 membranes in a BLB-dependent manner. Visualization was achieved either after autoradiograph of metabolically labelled proteins with [35S]methionine or by silver staining of larger preparations. In other experiments, elution of BLB-receptor complexes bound to streptavidin beads was carried out at neutral pH and the eluted fraction was reconstituted into phospholipid vesicles. This procedure revealed [125I]GRP binding activity that exhibited saturability, specificity and a 1946-fold increase in specific activity.
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PMID:Bombesin receptor from Swiss 3T3 cells. Affinity chromatography and reconstitution into phospholipid vesicles. 217 13

To characterize directly the ability of cholecystokinin (CCK) to interact with receptors on the sphincter of Oddi (SO), we measured binding of 125I-labeled Bolton-Hunter-labeled COOH-terminal octapeptide of cholecystokinin (125I-BH-CCK-8) to tissue sections from the guinea pig SO. Autoradiography localized binding of 125I-BH-CCK-8 over the SO smooth muscle layer. Binding was saturable, specific, dependent on time, pH, and temperature, and was reversible. Binding of 125I-BH-CCK-8 was inhibited by various CCK receptor agonists with the following potencies: CCK-8 much greater than des(SO3)CCK-8 much greater than gastrin-17-I and by various CCK receptor antagonists with the following potencies: L-364,718 greater than proglumide analogue 10 much greater than carbobenzoxy-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-NH2 greater than N2,O2' dibutyryl guanosine 3',5'-cyclic monophosphate. The potencies of agonists in stimulating and of antagonists in inhibiting CCK-8-stimulated SO contractions correlated closely with their abilities to inhibit binding of 125I-BH-CCK-8. Analysis of binding of 125I-BH-CCK-8 to SO tissue sections revealed two classes of CCK binding sites: a high-affinity site [dissociation constant (Kd) 0.2 nM] and a low-affinity site (Kd 70 nM). Atropine or tetrodotoxin (TTX) caused a similar rightward shift of the CCK-8 dose-response curve for stimulation of SO contraction. Comparison of receptor occupation to CCK-8-induced contraction suggested that CCK-8 occupation of the high-affinity binding site correlated with contraction in the absence of atropine and the low-affinity CCK binding with contraction in the presence of atropine or TTX.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of cholecystokinin receptors on the sphincter of Oddi. 224 Feb 27

Neuronal pathways in the retrocerebral complex and thoracico-abdominal ganglionic mass of the blowfly Calliphora vomitoria have been identified immunocytochemically with antisera against the extended-enkephalins, Met-enkephalin-Arg6-Phe7 (Met-7) and Met-enkephalin-Arg6-Gly7-Leu8 (Met-8). Neurons of the hypocerebral ganglion, immunoreactive to Met-8, have axons in the crop duct nerve and terminals in muscles of the crop and its duct. Certain neurons of the hypocerebral ganglion are also immunoreactive to Met-7, and axons from these cells innervate the heart. Met-8 immunoreactive nerve terminals invest the cells of the corpus allatum. The source of this material is believed to be a single pair of lateral neurosecretory cells in the brain. There is no Met-7 immunoreactive material in the corpus allatum. In the corpus cardiacum neither Met-7 nor Met-8 immunoreactivity is present in the cells. However, in the neuropil of the gland certain fibres, with their origins elsewhere, do contain Met-8 immunoreactivity. The most prominent neurons in the thoracic ganglion are the Met-7 immunoreactive ventral thoracic neurosecretory cells, axons from which project to neurohaemal areas in the dorsal neural sheath and also, via the ventral connective, to the brain. Co-localisation studies show that the perikarya of these cells are immunoreactive to antisera raised against several vertebrate-type peptides, such as Met-7, gastrin/cholecystokinin and pancreatic polypeptide. However, their axons and terminals show varying amounts of the peptides, suggesting differential transport and utilisation. Only a few cells in the thoracic ganglion are immunoreactive to Met-8 antisera. These lie close to the nerve bundles supplying the legs. In the abdominal ganglion, Met-8 immunoreactive neurons project to the muscles of the hindgut. This study suggests that the extended enkephalin-like peptides of Calliphora may have a variety of different roles: as neurotransmitter or neuromodulator substances; in the direct innervation of effector organs; and as neurohormones.
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PMID:Distribution of functional significance of Met-enkephalin-Arg6-Phe7- and Met-enkephalin-Arg6-Gly7-Leu8-like peptides in the blowfly Calliphora vomitoria. II. Immunocytochemical mapping of neuronal pathways in the retrocerebral complex and thoracic ganglion. 229 81

We have purified an acidic octapeptide from the neural ganglion of the protochordate Ciona intestinalis by a three-step procedure including C18 Sep-Pak fractionation, MonoQ ion-exchange chromatography, and C4 reversed-phase high-performance liquid chromatography. The purification was monitored by an immunoassay specific for the alpha-carboxyamidated COOH terminus common to the mammalian brain-gut hormones, cholecystokinin and gastrin. Automated Edman degradation revealed the sequence Asn-Tyr-Tyr-Gly-Trp-Met-Asp-Phe. In accordance with the high acidity of the peptide, amino acid analysis after cleavage with aminopeptidase M showed that both tyrosyl residues are sulfated. Hence, the structure is Asn-Tyr(SO3)-Tyr(SO3)-Gly-Trp-Met-Asp-Phe-NH2, as also confirmed by identity with the synthetic disulfated peptide in different chromatographic systems. The occurrence of two consecutively sulfated tyrosyl residues after a neutral residue challenges present concepts of consensus sites for tyrosyl sulfation. We conclude that the structure of the peptide, named cionin, suits that of a common ancestor for cholecystokinin and gastrin.
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PMID:Cionin: a disulfotyrosyl hybrid of cholecystokinin and gastrin from the neural ganglion of the protochordate Ciona intestinalis. 230 39

The formation of biologically active gastrin from glycine-extended processing intermediates occurs via the action of a peptide alpha-amidating enzyme. The observation that gastrin exists primarily as unamidated precursors in the pituitary but as amidated gastrin in the antrum prompted these studies to examine whether the amidating enzymes in the two organs were different in their characteristics. Furthermore, the amidating enzyme in the stomach has not previously been characterized in extensive detail. Amidating activity was quantified by measuring the conversion of Tyr-Gly-Trp-Met-Asp-Phe-Gly (glycine-extended hexagastrin) to Tyr-Gly-Trp-Met-Asp-Phe-NH2 (amidated hexagastrin) by radioimmunoassay. The activity of the antral enzyme in both the rat and hog had a similar apparent molecular weight (45,000-60,000), cofactor requirements (copper, ascorbic acid, and catalase), pH optima (5.5-8.5), and Km (12 microM) as the pituitary enzyme. These data suggest that antral and pituitary peptide alpha-amidating enzymes are the same enzyme, thus it is unlikely that differences in amidating enzymes can account for the observed differences in the tissue specific processing of gastrin.
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PMID:Characterization of gastrin amidation in the rat and porcine antrum: comparison with the pituitary. 234 64

The C-terminal tetrapeptide, Trp-Met-Asp-Phe-NH2, is a full agonist of gastrin, but des-Phe analogues, including Boc-Trp-Met-Asp-NH2, are antagonists. To ascertain the minimum structural requirement for an antagonist, we used conventional solution phase methodology to synthesize analogues with further modifications including removal of the alpha-amino group of Trp, conversion of the indole to a phenyl ring, and methylation of amide bonds. These analogues were tested for their effect on pentagastrin-stimulated acid release in dogs surgically prepared with a gastric fistula. When infused intravenously at a dose of 20 pmol kg-1 h-1, the peptides significantly inhibited acid secretion. The extent of inhibition ranged from 12% to 60%. Thus, tripeptide analogues based on the C-terminal sequence of gastrin act as potent and specific antagonists of gastrin-stimulated acid secretion.
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PMID:Novel C-terminal gastrin antagonists. Synthesis and biological activity. 234 51

Concentrations of gastrointestinal neuropeptides in serial human milk samples from 28 women were determined over the first 6 postpartum mo. All gut neuropeptides were present during the first postpartum week. Gastric inhibitory peptide (GIP) concentration remained constant but the others decreased by 6 wk. Bombesin concentration in breast milk was threefold greater than concurrent plasma concentration (p less than 0.001); all other neuropeptides were at the same or lower concentrations in milk than in plasma. At 36 wk gestation plasma concentrations of GIP were lower and concentrations of vasoactive intestinal peptide were higher than concentrations in age-matched control subjects. Concentrations of gastrin and cholecystokinin, bombesin, peptide histidine methionine, peptide YY, and neurotensin in plasma were similar in pregnant and nonpregnant women. These gut neuropeptides in milk may be important for growth and maturation of the gastrointestinal system in neonates. Bombesin may contribute to neonatal hypergastrinemia.
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PMID:Postpartum changes in pattern of gastrointestinal regulatory peptides in human milk. 234 35

An approach to the solid-phase segment condensation synthesis of the 17-peptide amide human gastrin-I has been developed. N alpha-amino and side-chain protection were provided by 9-fluorenylmethyloxycarbonyl (Fmoc) and tert.-butyl groups, and a series of anchors cleavable under mild conditions were used. The N-terminal pentapeptide pGlu-Gly-Pro-Trp-Leu-OH was prepared using a p-alkoxybenzyl ester linkage made by a preformed handle strategy. Cleavage, in 65% yield, was with the new Reagent M: CF3COOH-CH2Cl2-beta-mercaptoethanol--anisole (70:30:2:1), which was optimized to preserve the labile tryptophan residue. A new preformed handle procedure expedited solid-phase synthesis of the protected "middle" hexapeptide, Fmoc-(Glu(OtBu]5-Ala-OH, anchored as an o-nitrobenzyl ester. Chains were not lost during this assembly, and final photolytic cleavage (350 nm) in toluene--CF3CH2OH (4:1) occurred in 59% yield. Both protected intermediates were purified by simple gel filtration, whereupon they were shown to be pure by analytical HPLC, and gave satisfactory NMR and FABMS spectra. Last, the C-terminal hexapeptide, Tyr(tBu)-Gly-Trp-Met-Asp(OtBu)-Phe, was assembled on a tris(alkoxy)benzylamide "PAL" support. For the polymer-supported segment condensation, the middle and N-terminal pieces were added respectively in greater than 98% and 89% yields (judged by amino acid analysis and solid-phase sequencing), by overnight couplings in N,N-dimethylformamide (DMF) mediated by benzotriazolyl N-oxytrisdimethylaminophosphonium hexafluorophosphate (BOP) in the presence of 1-hydroxybenzotriazole (HOBt) and N-methylmorpholine (NMM). Racemization was 4% and 11% respectively at Ala and Leu. Cleavage with Reagent M followed by reversed-phase chromatography gave pure gastrin-I in an overall 30% isolated yield. These results compare favorably with those from a stepwise assembly.
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PMID:Orthogonal solid-phase synthesis of human gastrin-I under mild conditions. 240 94

Galanin was infused intravenously in 8 healthy volunteers at a dose of 40 pmol/kg.min for 1 h to investigate the pharmacologic effects of this peptide on postprandial gastrointestinal motility and gut peptide release in humans. Galanin strongly inhibited gastrointestinal motility. Gastric emptying was significantly delayed, with the time taken to empty 50% of the gastric contents increasing from 59.0 +/- 4.8 min (control infusion) to 99.3 +/- 4.7 min (galanin infusion). Mouth-to-cecum transit time increased from 67.5 +/- 6.9 to 126.3 +/- 18.5 min. Galanin potently suppressed the initial postprandial rise in plasma concentrations of glucose, insulin, peptide tyrosine tyrosine, neurotensin, enteroglucagon, pancreatic glucagon, somatostatin, and pancreatic polypeptide, but did not change gastric inhibitory polypeptide, motilin, peptide histidine methionine, and gastrin concentrations compared with control. The results indicate that an infusion of galanin has potent effects on the gastrointestinal tract in humans. The changes in motor activity in particular suggest that the local galaninergic innervation could have an important physiologic role in the control of human gastrointestinal propulsive motor activity.
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PMID:Inhibitory effect of galanin on postprandial gastrointestinal motility and gut hormone release in humans. 247 97

Nervous and endocrine peptidergic structures in human Brunner's glands were studied by immunofluorescence. Endocrine cells storing immunoreactive components respectively similar to somatostatin 14, the amino-terminal portion (1-14) of somatostatin 28, gastrin-cholecystokinin, and peptide YY were distributed throughout the acini. Peptidergic nerve structures contained materials immunologically related to vasoactive intestinal peptide, peptide histidine methionine, substance P, neuropeptide Y, and gastrin-releasing peptide. The latter peptide was detected in discrete fibers running into the acini but within no cell body in the submucosa. All other neuropeptides were stored in fibers, isolated or grouped in bundles, and in perikarya of submucosal ganglia close to the acini. No immunoreactive structures were detected using antisera directed against pancreatic polypeptide, secretin, motilin, neurotensin, or calcitonin gene-related peptide. The results suggest that several regulatory peptides may be involved in the control of Brunner's glands in humans.
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PMID:Immunocytochemical study of peptidergic structures in Brunner's glands. 247 87


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