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)

Using a newly developed radioimmunoassay for porcine gastrin-releasing peptide in plasma, we studied the pharmacokinetics of this peptide after infusing it into pigs at two dose levels. The disappearance of the peptide from plasma was characterized by two components, a fast one (t 1/2 1.4 min) and a slow one (t 1/2 6.6 min). With the same assay the release of gastrin releasing-peptide from the stomachs of 8 pigs that had been catheterized for selective sampling of fundic and antral blood was studied during vagal and splanchnic stimulation with or without acute adrenalectomy at neutral, acidic, and alkaline intragastric pH. Electrical stimulation of the vagal nerves resulted in a marked increase in both antral and fundic gastrin-releasing peptide release, whereas splanchnic stimulation was without effect. The effects of nerve stimulation were neither influenced by intragastric pH nor by adrenalectomy. Because of its presence in nerves in all layers of the gastric wall, its potent effect on gastrin release, and its release after vagal stimulation, gastrin-releasing peptide is likely to play a role in the vagal control of gastrin release, gastric motility, and acid secretion.
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PMID:Radioimmunoassay, pharmacokinetics, and neuronal release of gastrin-releasing peptide in anesthetized pigs. 673 80

Gastrin-releasing peptide (GRP) was infused at two dose levels [GRP I (0-30 min): bolus dose of 1.41 pmol kg-1, followed by 0.12 pmol kg-1 min-1; GRP II (30-60 min): bolus dose of 5.67 pmol kg-1, followed by 1.50 pmol kg-1 min-1] to six normal men to study the pharmacokinetics of GRP using a newly developed RIA and the effect of GRP on gastro-entero-pancreatic hormones and gastric acid secretion. The half-life of disappearance of GRP was 2.8 +/- 0.4 min (+/- SEM). The MCR and the apparent space of distribution were 33.0 +/- 4.0 ml kg-1 min-1 and 133 +/- 31 ml kg-1, respectively. GRP stimulated the secretion of gastrin, pancreatic polypeptide, insulin, glucagon, and glucose-dependent insulinotropic polypeptide in a dose-dependent manner. Gastric acid secretion was stimulated 15 min after the increase in gastrin secretion, suggesting that GRP stimulated gastric acid secretion via release of gastrin. GRP had no significant effect on the secretion of enteroglucagon or neurotensin. In the mammalian gastrointestinal tract, GRP is localized exclusively to nerve tissue. This fact and its potent effects demonstrated here make it a likely candidate for peptidergic nervous control of gastrointestinal function.
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PMID:Gastrin-releasing peptide: pharmacokinetics and effects on gastro-entero-pancreatic hormones and gastric secretion in normal men. 673 5

Porcine intestinal gastrin-releasing peptide (GRP) has been demonstrated to be structurally identical to the previously characterized gastric GRP. Ion-exchange and high-performance liquid chromatography of porcine intestinal extracts have identified two variant GRP forms. Studies on one of these variant forms suggest that a beta-aspartyl shift has occurred in the Asn-His structure of GRP; such a modification in an Asn-His structure occurring in a natural peptide or protein has not been previously reported. This variant GRP, although retaining bioactivity, appears to have reduced potency in elevating canine plasma gastrin levels.
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PMID:Identification and characterization of variant forms of the gastrin-releasing peptide (GRP). 685 67

The effect on plasma gastroenteropancreatic hormone levels on infusing the porcine gastrin-releasing peptide and bombesin into dogs demonstrated no qualitative difference in the spectrum of activity of the two peptides. Sustained elevation in plasma immunoreactive gastrin, pancreatic polypeptide, enteroglucagon, gastric inhibitory polypeptide, pancreatic glucagon and transient elevations in plasma insulin were seen during infusions of both peptides. The similar spectrum of activities and the structural homology between the two peptides suggests that the porcine gastrin releasing peptide is the porcine counterpart of the amphibian peptide bombesin.
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PMID:A qualitative comparison of canine plasma gastroenteropancreatic hormone response to bombesin and the porcine gastrin-releasing peptide (GRP). 702 73

The amino acid sequences of gastrointestinal hormones were compared in fragments of variable spans. Similarities within each of three peptide groups are extensive, but non-unique alignments were also noticed in the glucagon group. Use of different spans demonstrated that structural similarities are unevenly distributed in the gastrin family. Correct phasing was detected even for proteins with few identities and multi-shifted alignments (alcohol dehydrogenases). Tests for alignments among different groups of peptides revealed similarities between bombesin and glucagon or secretin, as well as between caerulein and litorin. Recently determined extended structures suggested the presence of a few deletions/insertions close to the middle of the molecules (two such positions missing in the gastrin-releasing peptide in relation to glucagon). The alignments appear to structurally link large groups of peptide hormones and active peptides. Similarities concentrate in the C-terminal parts, and gaps in the middle. These facts are consistent with known correlations with bioactivities. They also suggest the possibility of evolutionary connections among different peptides as well as corresponding relationships among their receptors.
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PMID:Structural similarities among gastrointestinal hormones and related active peptides. 709 53

The heptacosapeptide amide corresponding to the entire amino acid sequence of chicken gastrin-releasing peptide (cGRP) was synthesized similarly to the synthesis of porcine GRP by assembling six peptide fragments followed by deprotection with 1 M trifluoromethanesulfonic acid-thioanisole in TFA. A new carboxyl-activating reagent, thiazolidine-2-thione, was preferentially adopted for preparation of necessary fragments. The synthetic cGRP, purified by ion-exchange chromatography, followed by partition chromatography, was active as the synthetic porcine GRP, when plasma immunoreactive gastrin level was examined in rats. No obvious difference was observed when synthetic and natural cGRP preparations were compared by HPLC, immunochemical property and biological activity in dogs.
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PMID:Studies on peptides. CXI. Synthesis of chicken gastrin-releasing peptide. 712 60

Gastrin-releasing peptide is a 27-amino acid peptide recently isolated from porcine gut. It shares a common C-terminal decapeptide homology with bombesin (except for a His/Gln interchange at residue 8 from C-terminus). Synthetic porcine gastrin-releasing peptide was shown to release gastrin 5 min after intravenous injection in rats. Given intracisternally (0.3--3 microgram), but not intravenously (1--10 micrograms), gastrin-releasing peptide caused a dose-dependent reduction in gastric secretion (volume and acidity) and elevation in plasma gastrin levels measured 2 h after peptide injection and pylorus ligation in rats. Gastrin-releasing peptide given intracisternally had long acting, reversible, and specific inhibitory effects. Gastrin-releasing peptide blocked the secretion of acid evoked by 2-deoxy-D-glucose or TRH given intracisternally or by histamine given subcutaneously. The acetylated C-terminal octapeptide fragment of gastrin-releasing peptide inhibited gastric acid secretion as effectively as gastrin-releasing peptide. Acetylated C-terminal heptapeptide did not. These results demonstrated that gastrin-releasing peptide has the capability to act in the brain to inhibit basal and stimulated gastric secretion and its antisecretory effect does not depend on a decrease in gastrin release. The presence of bombesin immunoactivity in rat brain and its ability to act through the brain to inhibit gastric acid secretion suggest that bombesinlike peptides may be chemical messengers involved in central nervous regulation of gastric secretion.
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PMID:Central nervous system inhibition of gastric secretion in the rat by gastrin-releasing peptide, a mammalian bombesin. 723 37

Receptors for regulatory peptides (hormones or neurotransmitters) play a pivotal role in the ability of cells to taste the rich neuroendocrine environment of the gut. Recognition of low concentration of peptides with a high specificity and translation of the peptide-receptor interaction into a biological response through different signalling pathways (adenylyl cyclase-cAMP or phospholipase C-phosphatidylinositol) are crucial properties of receptors. While many new receptors have been identified and thereafter characterized functionally during the 1980s, molecular biology now emerges as the privileged way for the structural characterization and discovery of receptors. Different strategies of receptor cloning have been developed which may or may not require prior receptor purification. Among cloning strategies that do not require receptor purification, homology screening of cDNA libraries, expression of receptor cDNA or mRNA in Xenopus laevis oocytes or in COS cells, and the polymerase chain reaction method achieved great success, e.g. cloning of receptors for cholecystokinin, gastrin, glucagon-like peptide 1, gastrin-releasing peptide/bombesin, neuromedin K, neuropeptide Y, neurotensin, opioids, secretin, somatostatin, substance K, substance P and vasoactive intestinal peptide. All these receptors belong to the superfamily of G-protein-coupled receptors which consist of a single polypeptide chain (350-450 amino acids) with seven transmembrane segments, an N-terminal extracellular domain and a C-terminal cytoplasmic domain. In this chapter, we have detailed the properties of three receptors which play an important role in digestive tract physiology and illustrate various signal transduction pathways: pancreatic beta-cell galanin receptors which mediate inhibition of insulin release and intestinal epithelial receptors for vasoactive intestinal peptide and peptide YY, which mediate the stimulation and inhibition of water and electrolyte secretion, respectively.
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PMID:Receptors for gut regulatory peptides. 751 Sep 49

The short-chain pseudopeptide, [D-Phe6, Leu13 psi (CH2NH)Leu14]bombesin(6-14) (RDI), is reported to be a potent antagonist of bombesin, and development of this type of compound has greatly contributed to the investigation of biological actions of bombesin and its related peptides. We recently synthesized (E)-alkene bombesin isostere by replacing the peptide bond with an (E)-double bond: [D-Phe6, Leu13 psi [(E)CH = CH]Leu14] bombesin(6-14) (EABI). The present study examined the effect of EABI on amylase release from rat pancreatic acini. EABI showed no agonistic activity at concentrations up to 1 microM, and RBI showed slight agonistic activity at concentrations > 10 nM. EABI caused a dose-dependent inhibition of amylase release stimulated by 0.1 nM bombesin, with an IC50 of 6.7 +/- 1.7 nM, and induced almost-complete inhibition at 0.3 microM. RDI caused a dose-dependent inhibition of amylase release, with an IC50 of 68.7 +/- 16 nM. EABI caused a parallel and rightward shift of the entire dose-response curve of bombesin-stimulated amylase release, and the degree of the shift was dependent on the concentrations of EABI. EABI (100 nM) and RDI (100 nM) inhibited amylase releases stimulated by gastrin-releasing peptide (1 nM) and neuromedin-C (1 nM). In contrast, amylase release stimulated by cholecystokinin octapeptide (0.1 nM), carbachol (10 microM), vasoactive intestinal peptide (1 nM), and gastrin-17 (10 nM) was not inhibited by EABI and RDI. The results indicate that EABI is a potent and specific bombesin receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of a new bombesin receptor antagonist, (E)-alkene bombesin isostere, on amylase release from rat pancreatic acini. 754 72

Gastrin has a potent influence on gastric acid secretion and mucosal growth but its role in mucosal integrity has been little studied. This study investigated in rats whether gastrin protects the gastric mucosa against the damage by 100% ethanol and what are the possible mechanisms of this protection. Exogenous gastrin-17 (0.6-5.0 pmol/kg) injected subcutaneously (s.c.) reduced dose dependently ethanol-induced mucosal damage and the dose decreasing the ethanol lesions by 50% was about 1.8 pmol/kg. The protection afforded by gastrin-17 was accompanied by a dose-dependent increase in gastric blood flow and these effects were almost completely abolished by the pretreatment with specific CCKB (L-365,260) but not CCKA receptor antagonist (loxiglumide). Endogenous gastrin released by intragastric (i.g.) peptone meal or s.c. injection of gastrin-releasing peptide prevented the formation of acute ethanol-induced lesions and these effects were also abolished by the pretreatment with L-365,260 but not by loxiglumide. The inhibition of nitric oxide (NO) synthase, by NG-nitro-L-arginine methyl ester almost completely eliminated both the protective and hyperemic effects of gastrin-17 and the addition of L-arginine (but not D-arginine) to NG-nitro-L-arginine-methyl ester restored, in part, these effects of gastrin-17. Deactivation of sensory nerves with capsaicin did not influence the protective or hyperemic effects of gastrin-17. We conclude that both exogenous and endogenous gastrin exert its protective activity against ethanol damage of gastric mucosa and this effect is mediated through the interaction with specific CCKB receptors and arginine-NO pathway, but does not involve sensory nerves.
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PMID:Role of endogenous gastrin in gastroprotection. 758 56


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