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 responses of 122 neurons in the area postrema of anesthetized dogs to 17 common transmitters and peptides were determined. Recordings were made from one barrel of a seven-barrel ionophoretic electrode. All neurons were silent at rest, but most could be detected and excited by the application of glutamate. The glutamate response was a brief, high-frequency response of less than 1-sec duration. Excitatory responses were also found to histamine, norepinephrine, serotonin, dopamine, apomorphine, angiotensin II, neurotensin, leucine enkephalin, vasoactive intestinal polypeptide, thyrotropin releasing hormone, gastrin, vasopressin, and substance P. While most neurons tested were excited by dopamine and apomorphine, approximately half of those studied were also excited by each of the other substances. Inhibitory responses were found to norepinephrine (6 of 15 cells) and histamine (3 of 45 cells). No responses were found to acetylcholine, somatostatin, or cholecystokinin. The responses to all 13 excitatory substances other than glutamate were similar. Typically these responses had a latency of 2-20 sec and lasted for 30 sec to 5 min on their first application. The frequency of discharge was usually low (approximately 0.5 Hz). Multiple applications of these agents often induced a maintained spontaneous discharge of low frequency. Each application also induced a transient incremental discharge at a frequency that rarely exceeded 2 Hz. The area postrema has been proposed to be the "chemoreceptor trigger zone" for emesis (Borison and Wang, 1953). All of the agents which excite area postrema neurons, with the exception of serotonin and norepinephrine, are emetic, while none of the three agents without excitatory effects is known to be emetic. Thus these results provide strong support for the central role of the area postrema in emesis. The similarity of response to so many substances on small neurons suggests a common ionic and/or metabolic mechanism underlying the response. The prolonged nature of the response to brief administration of these agents would seem to be appropriate for neurons which subserve a sensation and behavior such as nausea and vomiting.
Cell Mol Neurobiol 1983 Jun
PMID:Responses of neurons of canine area postrema to neurotransmitters and peptides. 614 78

Antibodies against human prealbumin (HPA) give a strong immunoperoxidase staining of the A (glucagon) pancreatic cells and of glucagon-, insulin- and gastrin-producing pancreatic tumours. The majority of intestinal and bronchial carcinoids are also reactive. The staining may be related to presence in the C-terminal sequence of HPA of determinants in common with polypeptide (pro-) hormones.
Virchows Arch B Cell Pathol Incl Mol Pathol 1984
PMID:Binding of antibodies against human prealbumin to intestinal and bronchial carcinoids and to pancreatic endocrine tumours. 614 57

The effects of alterations in availability and access of extracellular media calcium on antral gastrin release were examined in the basal state and in response to cholinergic stimulation in rat antral organ culture experiments. In the presence of either divalent cationic chelator (EGTA) or calcium channel blocker (verapamil, nifedipine), carbachol-stimulated gastrin release was inhibited completely to values that were not significantly different from non-stimulated control. In the absence of added calcium chloride, carbachol stimulated gastrin release during the initial 30 min of culture but not at 69 and 120 min of culture. Inhibition by EGTA and verapamil of carbachol-stimulated gastrin release during the initial 30 min of culture suggests, but does not prove, that these agents may also effect intracellular availability and movement of calcium. Cholinergic stimulation of gastrin release demonstrated a concentration-dependent relationship with extracellular calcium: optimal culture media calcium concentration was 1 mM. In conclusion, these studies indicate that cholinergic stimulation of the gastrin cell requires availability of extracellular calcium.
Mol Cell Endocrinol 1984 Sep
PMID:Effects of calcium on cholinergic-stimulated gastrin release in the rat. 643 84

The effects of electrical stimulation of the vagus at varying pulse widths on the release of immunoreactive VIP (IR-VIP) and IR-gastrin have been investigated, using the isolated perfused rat stomach preparation. Electrical stimulation of vagal trunks at a pulse width of 0.1 msec duration yielded no change in basal IR-VIP levels whereas a pulse width of 5.0 msec produced a prompt sustained increase. Stimulation at either pulse width evoked gastrin release. Atropine blocked the vagal release of IR-gastrin but not IR-VIP whereas hexamethonium blocked both responses. Exogenously administered porcine VIP, at concentrations mimicking endogenously released levels, was used in an attempt to reproduce the effects observed by vagal stimulation. Exogenous VIP had no effect on gastrin or somatostatin-like immunoreactivity (SLI) release. These in vitro studies support a role for VIP as a neurotransmitter released from the stomach by low-threshold non-cholinergic vagal fibres, but involving autonomic ganglia.
Mol Cell Endocrinol 1981 Aug
PMID:Vagal release of IR-VIP and IR-gastrin from the isolated perfused rat stomach. 727 50

To identify the transcription termination elements in the mouse gastrin gene, we examined RNA transcripts after stable transfection of gastrin expression plasmids into the NIH3T3 cell line. The GT-repeat region at the 3'-flanking sequence of the mouse gastrin gene acted as a transcription terminator. When the GT-repeat unit was deleted from its site, the effect of termination disappeared. Further experiment, using serial deletion mutants, revealed that the 56-38 nucleotide upstream region from the GT-repeat unit also participated in transcription termination. We propose that the upstream region of the GT-repeat unit might be recognized as a pause site by the RNA polymerase II, and an abnormal DNA structure, derived from the GT-repeat unit, might function as a blockage of polymerase processivity.
Biochem Mol Biol Int 1995 May
PMID:Sequences responsible for transcription termination of the mouse gastrin gene. 749 58

To investigate the hypothesis that gastrin might be synthesized by tumour tissues in cancer of the colon, samples from six human colon tumours, one hepatic metastasis, four normal colonic mucosal samples and two antral and one fundic gastric mucosal samples from nine patients were analysed to determine whether gastrin mRNA was present. RNA was extracted from surgical specimens by ultracentrifugation on a CsCl cushion, purified using the guanidinium thiocyanate method, reverse-transcribed and amplified by polymerase chain reaction. Gastrin mRNA was detected in each colonic carcinoma sample (including the hepatic metastasis), while no such signal was observed in normal colon biopsies. Positive and negative controls (gastric antrum and fundus respectively) gave the expected results. In each of the positive samples, the chemiluminescent revelation of amplified products after Southern blotting corresponded to gastrin mRNA without the intron. These findings demonstrate the ability of primary and metastatic human colonic tumours to produce gastrin mRNA. Since malignant cell lines have been reported to produce gastrin peptide, and since gastrin receptors were present in some cases, our results support the idea that gastrin may be involved in an autocrine mechanism.
J Mol Endocrinol 1993 Oct
PMID:Detection of gastrin mRNA in fresh human colonic carcinomas by reverse transcription-polymerase chain reaction. 750 79

Gastrin is transcriptionally responsive to EGF stimulation (Merchant et al., 1991, Mol. Cell. Biol., 11:2686-2696). Consequently, we hypothesized that previously recognized gastrin autocrine loops (Hoosein et al., 1990, Exp. Cell. Res., 186:15-21), might be controlled by autocrine TGF alpha in human colon carcinoma cells. Therefore, we examined the interaction between these two autocrine growth factors in two colon carcinoma cell lines which utilize TGF alpha. The FET cell line requires exogenous TGF alpha/EGF for optimal growth and has a classical TGF alpha autocrine loop which is disrupted by TGF alpha or epidermal growth factor receptor (EGFr) antibodies. The HCT 116 cell line is not dependent on exogenous TGF alpha/EGF and exhibits a nonclassical TGF alpha autocrine loop which is not disrupted by neutralizing antibodies to either TGF alpha itself or the EGFr. Basal gastrin mRNA production is significantly higher in HCT 116 than FET as measured by RNase protection assay. In the FET cells, exogenous EGF stimulates gastrin mRNA production but not in HCT 116. When the TGF alpha autocrine loop in HCT 116 is disrupted by constitutive expression of antisense TGF alpha mRNA, the gastrin mRNA level is significantly repressed. In xenografts derived from these antisense clones, TGF alpha reverted to high expression, and the gastrin mRNA level was again increased. This interaction between the strong TGF alpha loop in HCT 116 and the gastrin autocrine loop may confer a growth advantage to these colon cells. Such interactions between growth factors may promote enhanced tumorigenicity to transformed cells with these strong, nonclassical autocrine loops.
 ...
PMID:Regulation of autocrine gastrin expression by the TGF alpha autocrine loop. 782 34

A novel series of 5-amino-1,4-benzodiazepin-2-one derivatives (amidines), which contain a cationic solubilizing group and which are antagonists for the cholecystokinin (CCK)-B receptor, have been identified. Optimization of this series led to the identification of an azabicyclononane amidine, L-740,093 [N-[(3R)-5-(3-azabicyclo[3.2.2]nonan-3-yl)-2,3-dihydro-1-methyl-2- oxo- 1H-1,4-benzodiazepin-3-yl]-N'-(3-methylphenyl)urea], that bound with high affinity of CCK-B receptors from guinea pig cerebral cortex (IC50 of 0.1 nM) and had a CCK-B/CCK-A receptor selectivity of 16,000. In comparison, L-365,260 had 85-fold lower affinity (8.5 nM) and was only 87-fold selective for CCK-B over CCK-A receptors. L-740,093 bound with high affinity to guinea pig gastrin receptors in vitro (IC50 of 0.04 nM). Electrophysiological studies on slices of rat ventromedial hypothalamic nucleus showed that L-740,093 produced rightward shifts of the concentration-response curve for the CCK-B receptor agonist pentagastrin (Kb of 0.06 nM). L-740,093 blocked pentagastrin-induced gastric acid secretion in anesthetized rats with a 50% inhibitory dose of 0.01 mg/kg, intraperitoneally, showing 100-fold greater activity, compared with L-365,260 (50% inhibitory dose of 1 mg/kg, intraperitoneally). An ex vivo binding assay in mice was used to investigate the interaction of L-740,093 with central CCK binding sites. After intravenous administration, L-740,093 inhibited ex vivo binding dose dependently, with a 50% effective dose of 0.2 mg/kg. These studies demonstrate that L-740,093 is the most potent and selective CCK-B antagonist yet described and that it has excellent central nervous system penetration.
Mol Pharmacol 1994 Nov
PMID:Biological properties of the benzodiazepine amidine derivative L-740,093, a cholecystokinin-B/gastrin receptor antagonist with high affinity in vitro and high potency in vivo. 796 84

Interactions between growth factor receptor systems may be important in the regulation of cell growth. The proliferation of pancreatic tumor AR42J cells has been shown to be stimulated by Epidermal growth factor (EGF) and gastrin and inhibited by somatostatin. To analyze the interaction between these different peptides, we explored the influence of EGF and gastrin on the somatostatin receptors. Treatment of AR42J cells with 10 nM EGF or gastrin for 24 hr increased specific binding of [125I] Tyr3SMS to 131 and 147% of that in control cells, respectively. The effect of peptides on [125I]Tyr3SMS binding was time- and dose-dependent, with half-maximal effect at 0.2 +/- 0.03 nM EGF and 0.3 +/- 0.15 nM gastrin. Scatchard plots revealed an increase in somatostatin receptor number of 27 and 80% after 48 hr of treatment with EGF and gastrin, respectively, without any change in receptor affinity. The increase in somatostatin receptor density was accompanied by the enhancement of biological responses to somatostatin. In cells pretreated with EGF or gastrin, the potency of somatostatin for inhibiting vasoactive intestinal peptide-stimulated cAMP content was increased 2-fold as that of somatostatin analog, SMS, for inhibiting cell proliferation. Furthermore, the efficiency of SMS as antiproliferative agent was greatly increased. Vasoactive intestinal peptide or forskolin did not modify [125I]Tyr3SMS binding of control or treated cells. The phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) did not affect [125I]Tyr3SMS binding. On the other hand, cycloheximide completely blocked the increase in [125I]Tyr3SMS binding induced by EGF and gastrin.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Pharmacol 1994 Jul
PMID:Up-regulation of somatostatin receptors by epidermal growth factor and gastrin in pancreatic cancer cells. 805 63

The nature and developmental profile of pancreatic gastrin and somatostatin were determined in the ovine fetus, a model considered relevant to human development. Gastrin and somatostatin peptide and mRNA were examined in the pancreas of fetal sheep at 80, 105, 125 and 140 days gestation (term: 145 days), 15-day-old lambs and adult sheep. Highest concentrations of gastrin (both amidated and the glycine-extended precursor) were observed in the lamb pancreas with gastrin mRNA levels highest at 140 days gestation. Amidated gastrin was present almost entirely as sulphated gastrin-17 while glycine-extended gastrin was mostly present as a high molecular weight form. Only glycine-extended gastrin was detected in the adult pancreas, indicating attenuated processing in mature adult pancreas. Up to 140 days gestation, gastrin mRNA correlated better with glycine-extended gastrin than with the amidated form, suggesting that amidation was a rate-limiting factor in the production of bioactive gastrin. Somatostatin mRNA and peptide reached a higher concentration and peaked before that of gastrin. Gastrin is a normal product of the fetal and adult pancreas although, when compared to the antrum, the levels are low and the processing to amidated forms is substantially reduced. Unlike in the stomach, the developmental profile of pancreatic gastrin and somatostatin does not appear to be linked.
Mol Cell Endocrinol 1993 May
PMID:Developmental expression of pancreatic gastrin and somatostatin in the sheep. 810 May 42


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