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)

To identify possible nuclear signals mediating long-term regulation of the pancreas by gastrointestinal hormones, the expression of c-fos, c-jun, and c-myc was investigated in rat pancreatic acini. Stimulation of the acini with cholecystokinin octapeptide (CCK-8, 100 pM), bombesin (10 nM), or carbachol (10 microM), but not gastrin (100 nM), secretin (100 nM), or vasoactive intestinal peptide (10 nM) induced an increase in oncogene mRNA expression. The percent increases of c-fos, c-jun, and c-myc mRNA were 207 +/- 40, 171 +/- 26, and 46 +/- 19 (n = 5) for CCK-8; 223 +/- 71, 159 +/- 31, and 43 +/- 21 (n = 5) for bombesin; and 125 +/- 51, 123 +/- 58, and 67 +/- 19 (n = 5) for carbachol, respectively. CCK-induced increases in oncogene mRNA were rapid and transient. c-fos and c-jun mRNA levels were increased after 30 min stimulation, peaked at 1 h, and returned to basal level in 2 h. Activation of c-myc was more prolonged with levels remaining elevated for at least 3 h. The effects of CCK-8 were concentration dependent. Detectable stimulation was seen at 10 pM; maximal stimulation occurred at 10 nM and was not affected by further increase in the concentration of CCK-8. JMV-180, a high-affinity site CCK receptor agonist and low-affinity site antagonist, alone did not stimulate c-fos mRNA expression but inhibited c-fos mRNA expression induced by CCK-8. These results suggest that the interaction between CCK and the low-affinity state of the CCK receptor is responsible for oncogene activation.
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PMID:CCK, bombesin, and carbachol stimulate c-fos, c-jun, and c-myc oncogene expression in rat pancreatic acini. 141 44

To evaluate whether pretreatment with prostaglandin E2 (PGE2) could desensitize pepsinogen secretion in chief cells from guinea pig, chief cells were pretreated with 10 microM PGE2 for up to 30 min. Desensitization of subsequent PGE2-stimulated secretion was maximal after 15 min, averaging only 29 +/- 9% (SE) of pepsinogen secretion in control cells stimulated with 10 microM PGE2. Desensitization was half-maximal with 30 nM PGE2. PGE2 pretreatment at 4 degrees C did not cause desensitization. In cells pretreated with 10 microM PGE2 for 15 min and then given 60 min to recover, responsiveness increased to 79 +/- 7% of that for control cells stimulated with PGE2. Thus the desensitization was reversible. Pretreatment with PGD2 and PGF2a did not alter subsequent PGE2-mediated secretion. PGE2-induced desensitization was heterologous but mediator specific because pepsinogen secretion was reduced in response to adenosine 3',5'-cyclic monophosphate (cAMP)-mediated agents (secretin and vasoactive intestinal peptide) but not Ca(2+)-mediated agents (CCK-8, gastrin, or carbachol). Pretreating chief cells with 10 microM PGE2 did not significantly alter cAMP generation in response to PGE2, secretin, or 3-isobutyl-1-methylxanthine, suggesting that desensitization was not mediated by an alteration in the receptor-coupled adenylate cyclase system. Because PGE2 pretreatment also desensitized pepsinogen secretion induced by the synthetic cAMP analogues 8-BrcAMP and 2'-O-monobutyryl-8-BrcAMP, it is likely that the ability of PGE2 to desensitize pepsinogen secretion in chief cells isolated from guinea pig is due to a mechanism distal to generation of cAMP.
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PMID:Prostaglandin E2 desensitizes cAMP-mediated pepsinogen secretion in chief cells. 165 22

The isolated gastric gland preparation, with aminopyrine accumulation as an index of the parietal cell response, has been used to study the effects of somatostatin (S-14), gastrin-releasing peptide (GRP), cholecystokinin (CCK-8), vasoactive intestinal peptide (VIP), and peptide YY (PYY) on the in vitro acid secretion in human and rabbit oxyntic mucosa. Somatostatin was able to inhibit the parietal cell response to histamine in both human and rabbit isolated gastric glands (maximal inhibition, 22% and 34%, respectively) but failed to inhibit the parietal cell response to db-cAMP. However, other peptides capable of inhibiting gastric acid secretion in vivo, such as CCK, VIP, and PYY, were unable to induce any inhibition of the parietal cell response to db-cAMP or histamine in the isolated gastric gland preparation irrespective of the species studied. GRP was not able to induce a parietal cell response, a finding that is in accord with the assumption that the stimulatory effect of GRP on gastric acid secretion in vivo is by releasing gastrin from antral G-cells.
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PMID:Effects of some gastrointestinal peptides on isolated human and rabbit gastric glands. 167 70

Two novel neuromedin C analogs [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C and [Leu9-psi-CH2NH-Leu10]neuromedin C, were synthesized by rapid solid phase methods and examined for their abilities to inhibit neuromedin C-stimulated amylase release by isolated rat pancreatic acini. Both analogs significantly inhibited maximally stimulated amylase release by neuromedin C in a dose-dependent manner with maximal inhibition seen at concentrations of 100 and 300 microM of [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C and [Leu9-psi-CH2NH-Leu10]neuromedin C, respectively. The IC50 (concentration required to half-maximally inhibit neuromedin C-stimulated amylase release) was 1.5 microM for [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C compared to a 13.4 microM IC50 for [Leu9-psi-CH2NH-Leu10]neuromedin C. The [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C analog produced a parallel rightward shift in the neuromedin C dose-response curve and Schild plots of the inhibition data gave a slope of 0.969 +/- 0.121 and a pA2 (apparent affinity for the acinar cell receptor in terms of neuromedin C receptor-stimulated amylase release) of 100 nM. While [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C significantly inhibited both neuromedin B- and gastrin releasing peptide-stimulated amylase release, the analog did not inhibit amylase release in response to either cholecystokinin octapeptide, vasoactive intestinal peptide, substance P, carbamylcholine, the Ca2+ ionophore A23187, forskolin, or 8-bromo-cyclic AMP. The results demonstrate that [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C is a potent, specific, and competitive antagonist for neuromedin C and peptides of the gastrin releasing peptide family and may serve as a useful molecule for exploring the physiological role of these peptides.
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PMID:[D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C antagonizes neuromedin C-stimulated amylase release by acini isolated from the rat pancreas. 169 79

Gastrin-releasing peptide (GRP) and bombesin can stimulate pepsinogen release by both gastrin-dependent and -independent mechanisms. Using isolated guinea pig gastric chief cells, we determined that GRP can act directly on the guinea pig chief cell to cause pepsinogen release. GRP and bombesin stimulated a 2.5- to 3-fold increase in pepsinogen release above basal release. Substance P also stimulated a small but significant increase in pepsinogen release. No gastrin immunoreactivity was detected in the supernatants of cells stimulated with up to 1 microM GRP or bombesin or 1 mM carbachol. GRP-stimulated pepsinogen release was completely inhibited by GRP/bombesin receptor agonists as well as substance P receptor antagonist but not by antagonists to receptors for gastrin, the octapeptide of cholecystokinin (CCK-8), secretin, vasoactive intestinal peptide (VIP), or muscarinic agents. Substance P-stimulated pepsinogen release was completely inhibited by substance P receptor antagonist but not by GRP/bombesin receptor antagonists. An additive effect on pepsinogen release was seen when GRP was combined with maximally effective concentrations of adenosine 3',5'-cyclic monophosphate (cAMP)-mediated agents (VIP, secretin, 8-BrcAMP) but not with calcium-mediated agents (carbachol, CCK-8, gastrin). These results indicate that GRP can directly stimulate pepsinogen release from guinea pig chief cells by a specific GRP receptor that mobilizes intracellular calcium.
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PMID:Gastrin-releasing peptide directly releases pepsinogen from guinea pig chief cells. 170 Jun 25

The arrangement of the enteric nerve plexuses in the colon of the guinea-pig and the distributions and projections of chemically specified neurons in this organ have been studied. Immunoreactivity for neuron specific enolase was used to examine the total population of neurons and individual subpopulations were studied using antibodies raised against calbindin, calcitonin gene-related peptide (CGRP), leu-enkephalin, gastrin releasing peptide (GRP), galanin, gamma aminobutyric acid, neurokinin A, neuropeptide Y (NPY), somatostatin, substance P, tyrosine hydroxylase and vasoactive intestinal peptide (VIP). Neuronal pathways within the colon were lesioned using myotomy and myectomy operations and extrinsic pathways running between the inferior mesenteric ganglia and the colon were also severed. Each of the antibodies revealed nerve cells and nerve fibres or only nerve fibres within the wall of the colon. VIP, galanin and GRP were in anally projecting pathways in the myenteric plexus, as they are in other species. In contrast, there are differences in the projection directions of enkephalin, substance P, NPY and somatostatin nerve fibres between regions and species. Surprisingly, somatostatin and NPY fibres have opposite projections in the small intestine and colon of the guinea-pig. The majority of nerve fibres that innervate the circular muscle, including fibres with immunoreactivity for VIP, enkephalin, substance P, NPY, galanin and GRP come from the myenteric ganglia. The mucosa is innervated by fibres from both the myenteric and submucous ganglia. The present results suggest that the guinea-pig distal colon is a suitable place in which to determine relations between structure, neurochemistry and functions of enteric neural circuits.
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PMID:Projections of chemically-specified neurons in the guinea-pig colon. 170 5

The levels of 10 regulatory peptides in acid-alcohol extracts of three regions of the small intestine (0-20%, 30-60%, and 70-100%, with respect to distance from the pylorus) have been monitored radioimmunometrically in sham-infected male (6-8 week old) C57 mice and mice given a 5-cysticercoid infection of the rat tapeworm Hymenolepis diminuta and autopsied 10 days postprimary infection and 5 days postsecondary infection (administered 28 days postprimary infection). The regulatory peptides examined were gastrin, gastrin-releasing peptide (GRP), glucagon (= enteroglucagon), motilin, neurotensin (NT), pancreatic polypeptide (PP), peptide histidine isoleucine (PHI), somatostatin (SRIF), substance P (SP), and vasoactive intestinal peptide (VIP). Statistical analyses revealed significant deviations from control values of five of the peptides (enteroglucagon and SP, both elevated; NT, PHI and VIP, all lowered) in intestinal tissue from infected mice; measurement of the same peptides in colonic extracts revealed no significant differences between infected and sham-infected mice. Parallel changes in peptide levels between normal infected and immunosuppressed infected mice were not evident, although elevations in the tissue levels of enteroglucagon and SP were found in infected Wistar rats (normal host). Results are discussed with respect to a peptidergic involvement in the pathology and host immune response to an intestinal tapeworm.
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PMID:Hymenolepis diminuta: changes in the levels of certain intestinal regulatory peptides in infected C57 mice. 171 77

The fasting plasma levels of 9 gastrointestinal regulatory peptides were measured by radioimmunoassay in 13 stable patients with chronic renal failure receiving hemodialysis treatment regularly and compared with those of 10 healthy controls. The plasma concentrations of gastrin-releasing peptide, motilin, neurotensin, pancreatic polypeptide, peptide YY, somatostatin, substance P, and vasoactive intestinal peptide were increased. The plasma level of gastrin was not statistically different from that of the controls (p = 0.077). We conclude that patients with chronic renal failure receiving hemodialysis treatment regularly have increased concentrations of eight of nine measured gastrointestinal regulatory peptides. The elevated levels of gastrointestinal peptides in patients with chronic renal failure may contribute to uremic gastrointestinal symptoms and dysfunctions. It is necessary to make a renal function evaluation before interpreting measured plasma levels of gastrointestinal regulatory peptides.
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PMID:Plasma levels of gastrointestinal regulatory peptides in patients receiving maintenance hemodialysis. 171 7

The effect of sepsis on plasma levels of various gut peptides was studied in rats. Sepsis was induced by cecal ligation and puncture (CLP); control animals underwent sham operation. Sixteen hours after CLP or sham operation, portal and systemic blood was drawn, and plasma levels of gastrin, vasoactive intestinal peptide (VIP), secretin, peptide YY (PYY), gastrin-releasing peptide (GRP), and substance P were determined by radioimmunoassay. Plasma levels of gastrin, VIP, PYY, and secretin were elevated in septic rats compared with nonseptic animals, with the highest levels noted in portal blood. There was no effect of sepsis on GRP or substance P levels. In other experiments, human recombinant interleukin 1 alpha (IL-1 alpha) or recombinant tumor necrosis factor alpha (TNF alpha) was injected intraperitoneally (300 micrograms/kg body weight in 3 divided doses over 16 hours). There was no change in plasma levels of gut peptides after IL-1 alpha injection. TNF alpha induced elevation of PYY levels in portal plasma with no change in other gut peptide levels. The results suggest that sepsis stimulates release of certain gut peptides and that TNF, but not IL-1, may be partly responsible for this response. The mechanism of the release of gut peptides and its significance in the pathophysiologic changes induced by sepsis remain to be determined.
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PMID:Effect of sepsis or cytokine administration on release of gut peptides. 173 67

HPLC-purified 125I-labeled vasoactive intestinal peptide (VIP) bound in a specific, saturable, and reversible manner to pancreatic plasma membranes isolated from newborn calves, from milk-fed calves at 28 and 119 days, and from weaned calves at 119 days. A series of VIP analogues, including pituitary adenylate cyclase-activating polypeptide (PACAP), displaced 125I-VIP binding and activated adenylate cyclase in the same order of relative potency: PACAP-38 greater than helodermin greater than VIP, PACAP-27 greater than PHM (human peptide with NH2-terminal histidine and COOH-terminal methionine amide). At maximally effective concentrations, these five peptides produced the same two- to threefold increase of adenylate cyclase activity in pancreatic membranes from newborn and 28-day-old calves, and fourfold in ruminant or preruminant animals at 119 days. The activation constant for PACAP-38 ranged from 0.1 to 0.34 nM throughout the postnatal development. Helospectin I and II were three times less potent than VIP in inhibiting 125I-VIP binding. At concentrations up to 0.1 microM, secretin, rat and human growth hormone-releasing factors, glucagon, oxyntomodulin, the truncated form of glucagon-like peptide-1 lacking the 6 NH2-terminal amino acid sequence (TGLP-1), GLP-2, gastric inhibitory peptide, gastrin, CCK, and insulin had no effect on binding. Scatchard plots from 28- and 119-day-old calves were compatible with the presence of two classes of 125I-VIP binding sites: one with a high affinity for VIP and a low binding capacity (Kd = 0.11-0.4 nM, Bmax = 66-174 fmol/mg protein) and the other with a low affinity and high binding capacity. At birth, only one class of binding sites was observed (Kd = 0.4 nM, Bmax = 858 fmol/mg protein). The covalently cross-linked PACAP-preferring 125I-VIP binding site is a glycoprotein of 55 kDa with higher sensitivity to PACAP vs. helodermin and VIP. Our results suggest that calf pancreatic functions might be regulated at an early stage of postnatal development by PACAP receptors linked to cAMP generation.
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PMID:Characterization of binding sites for VIP-related peptides and activation of adenylate cyclase in developing pancreas. 184 91


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