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)

Endocytosis of the gastrin releasing peptide receptor (GRP-R) may regulate cellular responses to GRP. We observed endocytosis in transfected epithelial cells by confocal microscopy using cyanine 3-GRP (cyanine 3.18-labeled gastrin releasing peptide) and GRP-R antibodies. At 4 degrees C, cy3-GRP and GRP-R were confined to the plasma membrane. After 5 min at 37 degrees C, ligand and receptor were internalized into early endosomes with fluorescein isothiocyanate-transferrin. After 10 min, cy3-GRP and GRP-R were in perinuclear vesicles, and at 60 min cy3-GRP was in large, central vesicles, while GRP-R was at the cell surface. We quantified surface GRP-R using an antibody to an extracellular epitope and an 125I-labeled secondary antibody. After exposure to GRP, there was a loss and subsequent recovery of surface GRP-R. Recovery was unaffected by cycloheximide, and thus independent of new protein synthesis, but was attenuated by acidotropic agents, and therefore required endosomal acidification. Internalization of 125I-GRP, assessed using an acid wash, was maximal after 10-20 min, and was clathrin-mediated since it was inhibited by hyperosmolar sucrose and phenylarsine oxide. Thus, GRP and its receptor are rapidly internalized into early endosomes and then dissociate in an acidified compartment. GRP is probably degraded whereas the GRP-R recycles.
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PMID:Direct observation of endocytosis of gastrin releasing peptide and its receptor. 787 31

Medullary thyroid carcinoma (MTC) can be important for gastroenterologists because 20-30% of patients with MTC suffer from chronic diarrhea and the tumor is capable of producing--besides other bioactive substances--a multitude of gastroenteropancreatic hormones. Gastrointestinal hormone profiles of 5 patients with MTC were determined both basally and after intravenous stimulation with secretin and calcium respectively. Diagnosis of MTC was confirmed histologically or cytologically and by demonstration of elevated serum concentration of calcitonin both basally and after calcium stimulation. 4/5 patients had chronic diarrhea. Normal values or only borderline increases were found for the following hormones: vasoactive intestinal polypeptide (VIP), neurotensin, substance P, growth hormone releasing hormone (GRH), glucagon, neurokinin A, peptide YY, and pancreatic polypeptide. Somatostatin was elevated after calcium stimulation in 1/5 patients only. The main findings were increased basal concentrations for GAWK in 5/5 patients and elevated concentrations for gastrin-releasing peptide (GRP, human bombesin) after calcium stimulation in 4/5. Probably as a consequence of the GRP increase, an increase in gastrin occurred in parallel, indicating bioactivity of the GRP released from the tumor. Besides calcitonin as the main tumor marker for MTC, determination of GAWK and GRP seems to provide helpful additional markers in laboratory diagnosis of MTC. GRP determination after i.v. calcium infusion allowed identification of patients with normal basal plasma GRP concentration.
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PMID:[Gastrointestinal hormone profile in medullary thyroid carcinoma]. 801 6

Suprachiasmatic nuclei (SCN) from hypothalami of postnatal rats were maintained for 18-39 days in vitro as organotypic slice explants. Neuronal subtypes containing vasopressin (VP), vasoactive intestinal polypeptide (VIP), gastrin releasing hormone (GRP), and GABA were immunocytochemically identifiable in these cultures. In situ hybridization histochemistry was compatible with these SCN slice explant cultures, and mRNA encoding for VP was detected bilaterally within these nuclei. After 18 days in vitro, both VP mRNA and VP immunoreactivity increased from levels present on postnatal days 4 (the earliest age from which the explanted tissue was derived) to levels typical of adult SCNs. In contrast, the GRP expression remained low, characteristic of early postnatal animals and far lower than adult levels. This suggests that the developmental cues or programs necessary for enhanced VP expression are maintained in these cultures, while those affecting GRP expression are absent or inhibited. VIP-containing neurons were numerous in the cultures. Culture slices appeared healthy, and similar numbers and distributions of identifiable neurons within the SCN were observed, whether or not the slices were grown in the presence of serum. EM analysis revealed that the SCN in vitro is composed of tightly packed neurons, processes, and abundant synapses containing both clear and dense core vesicles, closely resembling the SCN in vivo. Vasopressinergic neuronal somata contained extensive Golgi systems and labeled secretory granules, the latter organelle being present also within processes and synaptic terminals. GABA-immunopositive processes and synaptic profiles were abundant, with labeling occurring particularly over secretory vesicles and mitochondria. This slice culture system effectively maintained much of the intrinsic organization and cellular components of the SCN for long periods in vitro and should be an excellent model system for studying the intrinsic molecular mechanisms and extrinsic cues which regulate neuronal phenotype in this circadian pacemaker.
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PMID:Characterization of the suprachiasmatic nucleus in organotypic slice explant cultures. 835 7

In the past decade, over 1000 continuous human cell lines have been established from lung cancer biopsy specimens. Numerous growth factors and receptors have been identified in the small cell lung cancer (SCLC) cell lines. SCLC is a neuroendocrine tumor which contains numerous peptides, including bombesin/gastrin releasing peptide (BN/GRP), and receptors. High levels of GRP mRNA and immunoreactivity are present in SCLC cells. The secretion rate of GRP from SCLC cells is increased by vasoactive intestinal peptide (VIP), which elevates the intracellular cAMP. GRP binds to cell surface receptors, elevates cytosolic calcium and stimulates the growth of SCLC cells. Additional SCLC growth factors include insulin-like growth factor I (IGF-I) and transferrin. IGF-I mRNA and protein is present in SCLC. IGF-I binds with high affinity to SCLC cells and stimulates tyrosine kinase activity and growth. Transferrin is also present in SCLC cells. Transferrin binds with high affinity to SCLC cells and stimulates iron transport and growth. Synthetic peptide antagonists and monoclonal antibodies have been identified which disrupt autocrine growth pathways and inhibit SCLC growth.
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PMID:Growth factor and peptide receptors in small cell lung cancer. 838 84

Bombesin/gastrin releasing peptide (BN/GRP) receptors were solubilized and purified from human glioblastoma (U-118) and lung carcinoid cell lines (NCI-H720). The U-118 cells, when extracted with CHAPS/cholesterol hemisuccinate (CHS), bound (125I-Tyr4)BN with high affinity (Kd = 2 nM) to a single class of sites (Bmax = 150 fmol/mg protein). Specific (125I-Tyr4)BN binding was inhibited with high affinity by BN, GRP, GRP14-27, and receptor antagonists such as (D-Phe6)BN6-13methylester(ME) and (D-Phe6)BN6-13 propylamide(PA) (IC50 = 2, 22, 3, 1 and 2 nM, respectively) but not GRP1-16 or BN1-12. The solubilized and cellular receptor bound peptides with similar affinity. The solubilized receptor was purified using (Lys0, Gly1-4, D-Ala5)BN and (Lys3, Gly4,5, D-Tyr6)BN3-13 PA affinity resins. When eluted from the affinity resins by NaCl, the receptor bound (125I-D-Tyr6)BN6-13ME with high affinity. The NCI-H720 BN/GRP receptor was purified 86,000-fold after extraction with CHAPS/CHS and purification using both affinity resins. SDS-PAGE analysis indicated that major 65 and 115 kDa proteins were purified. These data indicate that BN/GRP receptors can be solubilized from human cells and purified using affinity chromatography techniques with retention of ligand binding activity.
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PMID:Solubilization and purification of bombesin/gastrin releasing peptide receptors from human cell lines. 839 Dec 95

The suprachiasmatic nuclei (SCN) of the rodent hypothalamus function as a light entrainable circadian pacemaker. The SCN contain moderate to high concentrations of a number of neuropeptides including peptides showing structural homology with the amphibian derived tetradecapeptide, bombesin (BN), called bombesin-like peptides (BNLPs). BNLPs include the 27 amino acid peptide, gastrin releasing peptide (GRP1-27), a smaller decapeptide (GRP18-27) and another decapeptide with less structural homology, neuromedin B (NmB). Immunoreactivity for BN and receptors for BNLPs have been demonstrated in the region of the rat SCN receiving photic input. We studied the effects of local pressure ejections of BNLPs dissolved in saline/1% bovine serum albumin (BSA) vehicle on the extracellularly recorded firing rates of Syrian hamster SCM neurons in a hypothalamic slice preparation. In one study, an ejecting electrode containing BN (10(-8) to 10(-4) M) was positioned 20 to 60 microm from a recording electrode. Of 74 cells tested with BN, 50 (67.6%) showed significant increases in firing rate, while 3 of 29 cells (15.8%) tested with vehicle ejections were activated. In a second study, a single electrode was used for both recordings and pressure ejections. Of 48 cells tested, BN (10(-6) to 10(-4) M) activated 30 (62.5%) and suppressed firing in 4 (8.3%). Of 208 cells tested with GRP1-27 (10(-9) to 10(-4) M), 105 (50.5%) were activated and 2 (1.0%) were suppressed. The percentage of cells responding increased with the concentration of GRP1027 used in the electrode. No circadian variation in responsiveness to GRP1-27 was detected. GRP18-27 (5 x 10(-5) to 10(-4) M) activated 10 out of 18 cells tested (55.6%), while NmB (10(-4) M) activated 2 out of 30 cells tested (6.7%) and vehicle ejections activated 1 out of 36 cells tested (2.8%). GRP1-27, GRP18-27 and BN, the BNLPs showing the greatest degree of structural homology, activate approximately 50% of SCN cells, apparently via the BN/GRP-preferring receptor subtype, and may play a role in photic entrainment.
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PMID:Electrophysiological effects of pressure-ejected bombesin-like peptides on hamster suprachiasmatic nucleus neurons in vitro. 868 Apr 27

Vagal preganglionic efferents to the rat stomach were labeled anterogradely by injecting the fluorescent carbocyanine dye DiA into the dorsal motor nucleus in vivo. Enteric neurons were labeled in toto by intraperitioneal administration of Fluorogold, and neurochemically characterized by simultaneous single- and double-label immunocytochemistry. Single peptide immunocytochemistry revealed that in all three major areas of the stomach, about one-third of all gastrin-releasing peptide immunoreactive (GRP-IR) neurons in the myenteric plexus, received vagal contacts. Because the proportion of GRP-IR neurons was 32% in the fundus, 23% in the corpus, and only 8% in the antrum, the absolute number of vagally contacted GRP-IR neurons per cm2 was also different. Double-label immunocytochemistry revealed colocalization of vasoactive intestinal peptide immunoreactivity (VIP-IR) in 45%, and of enkephalin immunoreactivity (ENK-IR) in about 30%, of the GRP-IR myenteric neurons. A subpopulation of myenteric neurons colocalized GRP-IR and VIP-IR and projects almost exclusively to the gastrin cell-rich basal mucosa of the antrum and the oxyntic mucosa of the corpus. Another subpopulation containing GRP-IR, but not VIP-IR, projects mainly to the myenteric plexus itself and the external muscle layers, particularly the longitudinal muscle. A third group of neurons containing VIP-IR but not GRP-IR projects heavily to the circular muscle layer, the muscularis mucosae, and to other myenteric neurons. Vagal input to these three subpopulations seems not to be selective, in that an equal proportion of about 20 to 30% of each group was vagally contacted. Vagal inputs to these neurochemically and topographically distinct enteric neurons provide the basis for the physiological vagal control of gastrin release, gastric acid secretion, and gastric motility.
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PMID:Morphological analysis of vagal input to gastrin releasing peptide and vasoactive intestinal peptide containing neurons in the rat glandular stomach. 879 57

Mammalian members of the bombesin-like peptide family (gastrin releasing peptides; GRP) have been localized in the ovine median eminence and in hypophysial-portal blood, suggesting a role in the regulation of anterior pituitary function. In this study we have shown that although bombesin cannot stimulate ACTH secretion alone, it potentiates release by ovine CRF, an effect blocked by the GRP receptor antagonist D-Tyr6bombesin (6-13) propylamide. Bombesin did not potentiate AVP-stimulated ACTH release; instead release was attenuated when bombesin was given at a 10-fold or greater molar excess over AVP, with no interaction seen at lower concentrations. We conclude that ovine corticotrophs express bombesin receptors, and that GRP may act in concert with other hypothalamic releasing factors to regulate ACTH secretion.
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PMID:Bombesin regulation of adrenocorticotropin release from ovine anterior pituitary cells. 935 57

Previous study showed that duodenal ulcer (DU) patients infected with Helicobacter pylori (H. pylori) have increased basal and pentagastrin- or GRP-induced gastric acid secretion and that these disturbances reversed fully after eradication of H. pylori. This study was designed to compare the gastric acid secretory profile, plasma gastrin levels and growth factors (EGF and TGF alpha) expression in gastric mucosa in DU patients with those in atrophic gastritis patients before and six months after verified eradication of H. pylori. In DU patients, basal and stimulated (GRP and pentagastrin) gastric acid secretion was significantly higher than in healthy controls. Six months following the eradication of H. pylori with triple therapy (omeprazole+clarithromycin+amoxicillin), this secretion returned to normal value. In contrast, in patients with atrophic gastritis, such eradication of H. pylori resulted in a significant increase in basal and pentagastrin- and GRP-stimulated acid secretion. Mucosal expression of immunoreactive EGF and TGF alpha was significantly enhanced in H. pylori positive DU and atrophic gastritis patients but this elevation disappeared or was markedly decreased 6 months upon the eradication of H. pylori. We conclude that 1) H. pylori infection is accompanied both in DU and atrophic gastritis patients by an enhanced plasma gastrin and increased mucosal expression of EGF and TGF alpha, 2) basal and GRP-induced acid secretion is significantly elevated in DU, whereas that in atrophic gastritis patients is greatly reduced, and 3) the H. pylori eradication restores gastric acid and plasma gastrin release as well as the mucosal expression of growth factors in DU and atrophic gastritis.
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PMID:Helicobacter pylori and impaired gastric secretory functions associated with duodenal ulcer and atrophic gastritis. 937 19

This study investigated the presence of the putative peripheral neuromodulators Gamma-aminobutyric Acid (GABA) and Bombesin/Gastrin-Releasing Peptide (BN/GRP) in the human tooth pulp. Caries free and asymptomatic carious teeth were processed for paraffin embedding and sectioned at six microns. From each specimen, sections were stained with hematoxylin and eosin; other sections were subjected to Avidin-Biotin-Peroxidase Complex immunohistochemistry for GABA and BN/GRP. Sections of rat brain and small cell lung carcinoma served as positive controls. Results indicate the presence of specific GABA-like and BN/GRP-like immunoreactivity within the pulps of both normal and carious teeth. Overall staining for both ligands was significantly more intense within inflamed pulps. Based on their actions elsewhere, GABA and BN/GRP may play a role in the dental pulp as peripheral neuromodulators or as growth factors.
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PMID:Immunohistochemical study of gamma-aminobutyric acid and bombesin/gastrin releasing peptide in human dental pulp. 959 54


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