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)

Biochemical assays on microdissected samples, denervation studies, subcellular fractionation, and light and electron microscopic autoradiography of high affinity uptake have been performed to study the cellular localization of transmitter candidates in the rat hippocampal formation. High affinity uptake of glutamate and aspartate is localized in the terminals of several excitatory systems, such as the entorhino-dentate fibres (perforant path), mossy fibres (from granular cells) and pyramidal cell axons. Thus, in stratum radiatum and oriens of CA1, 85% of glutamate and asparate uptake and 40% of glutamate and aspartate content are lost after lesions of ipsilateral plus commissural fibres from CA3/CA4. Hippocampal efferents also take up aspartate and glutamate, since these activities are heavily reduced in the lateral septum and mamillary bodies after transection of fimbria and the dorsal fornix. The synthesis (by glutamic acid decarboxylase), content and high affinity uptake of gamma-aminobutyrate (GABA) are not reduced after lesions of these or other projection fibre systems. A localization in intrinsic neurons is confirmed by a selective loss of glutamic acid decarboxylase after local injections of kainic acid. Peak concentrations of the enzyme occur near the pyramidal and granular cell bodies, corresponding to the site of the inhibitory basket cell terminals, and in the outer parts of the molecular layers. Some 85% of glutamic acid decarboxylase is situated in 'nerve ending particles'. Acetylcholine synthesis (by choline acetyltransferase) disappears after lesions of septo-hippocampal fibres. Since 80% of the hippocampal choline acetyltransferase is in 'nerve ending particles', the characteristic topographical distribution of this enzyme should reflect the distribution of cholinergic septo-hippocampal afferents. Serotonin, noradrenaline, dopamine and histamine are located/synthesized in afferent fibre systems. Some monoamine-containing afferents to the hippocampal formation pass via the septal area, others via the amygdala. The hippocampal formation also contains nerve elements reacting with antibodies against neuroactive peptides, such as enkephalin, substance P, somatostatin and gastrin/cholecystokinin.
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PMID:Localization of putative transmitters in the hippocampal formation: with a note on the connections to septum and hypothalamus. 3 19

The polyamines spermidine and spermine are essential for cell proliferation. Most growth factors stimulate polyamine synthesis by inducing ornithine decarboxylase activity, which catalyzes the formation of putrescine from ornithine. Putrescine can then be utilized either for polyamine biosynthesis or may serve as a substrate for diamine oxidase (DAO), leading to formation of gamma-aminobutyric acid (GABA). Growth of the oxyntic mucosa of the stomach is stimulated by feeding, by trophic hormones such as gastrin and by exogenous administration of putrescine. Conversely, fasting, as well as ornithine decarboxylase inhibition decrease oxyntic mucosal DNA synthesis. We now demonstrate that fasted rats show a high degree of [3H]GABA formation from [3H]putrescine in the oxyntic mucosa and that feeding or injections of gastrin, caerulein or the DAO-inhibitor aminoguanidine decrease such [3H]GABA formation and, instead, stimulate formation of [3H]spermidine. Moreover, gastrin injections reduced oxyntic mucosal DAO activity. Thus, oxyntic mucosal DAO activity is regulated by tropic factors and may be involved in growth regulation by controlling intramucosal putrescine metabolism.
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PMID:Regulation of gastric mucosal diamine oxidase activity by gastrin. 164 66

The effect of gamma-amino-n-butyric acid (GABA), the GABA(A) receptor agonist muscimol (5-aminomethyl-3-hydroxyisoxazole), and the GABA(B) receptor agonist baclofen [4-amino-3-(4-chlorophenyl)butanoic acid] on the incidence and number of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine was investigated in Wistar rats. Rats received alternate-day i.p. injections of 500 or 1000 mg/kg of body weight GABA, 0.25 or 0.5 mg/kg of body weight muscimol, or 4 or 8 mg/kg of body weight baclofen after 25 wk of p.o. treatment with the carcinogen. Prolonged administration of GABA at 1000 mg/kg of body weight, but not at 500 mg/kg of body weight, and of baclofen at 4 and 8 mg/kg of body weight significantly decreased the incidence and number of gastric cancers of the glandular stomach in Wk 52, but long-term muscimol administration had no influence. Histologically, GABA at the high dosage and baclofen at both dosages significantly decreased the labeling index of the antral mucosa and significantly increased the serum gastrin level. Furthermore, baclofen at both dosages significantly decreased antral pH and significantly increased gastric acid secretion. These findings indicate that GABA inhibits gastric carcinogenesis via the GABAB receptor and that this effect may be related to its effect in decreasing the proliferation of antral mucosa.
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PMID:Inhibition by gamma-amino-n-butyric acid and baclofen of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. 237 57

An ultrastructural immunocytochemical study was undertaken to identify neuroactive substances contained in presynaptic boutons in the hypothalamic suprachiasmatic nucleus. Axonal boutons containing immunoreactive gamma-aminobutyrate, glutamate decarboxylase, neurophysin/vasopressin, gastrin releasing peptide/bombesin, somatostatin and serotonin were localized within the hypothalamic suprachiasmatic nucleus with pre-embedding peroxidase immunostaining. Synaptic contacts were found between boutons containing each of these substances and postsynaptic structures. While some variation in synaptic morphology existed, most of the immunoreactive contacts were of the symmetrical type. Previous work has indicated that neuroactive peptides may be found in highest concentrations in dense-core vesicles, to examine the subcellular localization of the amino acid inhibitory transmitter gamma-aminobutyrate, ultrastructural immunocytochemistry with pre-embedding peroxidase was compared with post-embedding immunocytochemistry with colloidal gold. Ultracryothin sections were also used for ultrastructural localization of gamma-aminobutyrate and glutamate decarboxylase immunoreactivity. Both gamma-aminobutyrate and glutamate decarboxylase immunoreactivity were found throughout the cytoplasm of immunoreactive boutons when pre-embedding peroxidase was used; with post-embedding colloidal gold immunostaining, label was found over areas containing small clear vesicles, and over mitochondria of immunoreactive axons. At the dilutions used in this study, strongly immunoreactive gamma-aminobutyrate dendrites, boutons forming asymmetrical synapses, and cell bodies were not found. Differences between pre-embedding and post-embedding immunostaining may be due to antigen and label diffusion caused by mild fixation and membrane damage necessary for antisera penetration during pre-embedding immunostaining. These results suggest that gamma-aminobutyrate, gastrin releasing peptide, somatostatin and vasopressin are contained in axons making contact with neurons of the suprachiasmatic nucleus, and may function as neurotransmitters here. Since all of these substances can also be localized in perikarya within the suprachiasmatic nucleus, there is a strong possibility that at least some of the axons containing immunoreactivity for each of these substances may be involved in local circuit interactions between neurons within the suprachiasmatic nucleus.
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PMID:Gamma-aminobutyrate, gastrin releasing peptide, serotonin, somatostatin, and vasopressin: ultrastructural immunocytochemical localization in presynaptic axons in the suprachiasmatic nucleus. 242 91

The effect of gamma-aminobutyric acid (GABA) on basal and bombesin (BBS)-stimulated release of somatostatin (SLI) and gastrin from isolated perfused rat stomach was examined. In the control study, BBS at a dose of 10 nM significantly stimulated release of SLI and gastrin. Infusion of GABA (1-1000 nM) caused a depression of SLI release induced by BBS (10 nM) in a dose-dependent fashion. However, at doses used in this study GABA had no effect on either basal level of SLI and gastrin or BBS-elicited gastrin release. These results indicate that GABA can specifically modulate BBS-induced SLI release from rat stomach.
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PMID:Effect of gamma-aminobutyric acid on bombesin-evoked release of somatostatin and gastrin from isolated rat stomach. 256 10

To stimulate peripheral gamma-aminobutyric acid (GABA) receptors, GABA, which does not cross the blood-brain barrier, was administered to dogs with vagally innervated gastric fistulas at intravenous doses of 0, 0.66, 2, 6, 18, and 54 micrograms.kg-1.min-1. Mean gastric acid output increased from zero basally to 3.0 +/- 1.4 mmol/h during infusion of 54 micrograms.kg-1.min-1 GABA. Plasma somatostatin-like immunoreactivity decreased significantly below basal levels during infusion of 54 micrograms.kg-1.min-1 GABA (P less than 0.05). To stimulate central nervous system GABA receptors as well as peripheral GABA receptors, progabide, a GABA-receptor agonist, which readily crosses the blood-brain barrier, was injected intravenously. Mean acid output was 3.5 +/- 1.3 mmol/h after 20 mg/kg progabide and 0.6 +/- 0.5 mmol/h after its vehicle (P less than 0.05). Basal serum gastrin concentration increased significantly after progabide injection. Acid output during insulin-induced hypoglycemia was inhibited 59% by 30 mg/kg intravenous progabide. Progabide infusion also diminished or abolished circulating gastrin, somatostatin, and pancreatic polypeptide responses during insulin-induced hypoglycemia (P less than 0.05). Further studies were performed in dogs with a gastric fistula and a vagally denervated Heidenhain pouch to confirm that GABA-receptor stimulation affects acid secretion via peripheral pathways. Intravenous injection of baclofen (0.5 mg/kg), a GABAB-receptor agonist, increased acid secretion significantly from the gastric fistula and the Heidenhain pouch. These studies suggest that GABA may play a role in regulating gastric acid secretion and gastrointestinal and pancreatic endocrine function by both central and peripheral mechanisms.
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PMID:Effect of GABA on basal and vagally mediated gastric acid secretion and hormone release in dogs. 283 63

Specific somatostatin (SRIH) receptors on human pituitary adenoma cell membranes were characterized using [125I]Tyr11-SRIH as the radioligand. Specific binding of [125I] Tyr11-SRIH to adenoma cell membranes reached a steady state within 30 min at 25 C, and semilogarithmic analysis of the data revealed that the rate of the binding was linear at 25 C with a t1/2 of 13.2 min. Specific binding increased linearly with 5-160 micrograms plasma membrane protein. SRIH-14 and SRIH-28 inhibited [125I]Tyr11-SRIH binding to adenoma cell membranes with ID50S of 0.32 and 0.50 nM, respectively, while secretin, glucagon, gastrin, cholecystokinin-8, bombesin, TRH, LHRH, human GH-releasing factor-(1-44)-NH2, D-Ala2-met-enkephalin, gamma-aminobutyric acid and taurine did not significantly inhibit binding. All of 13 GH-secreting adenomas investigated had specific and high affinity SRIH receptors, with a dissociation constant (Kd) of 0.80 +/- 0.15 nM (mean +/- SEM) and a maximal binding capacity (Bmax) of 234.2 +/- 86.9 fmol/mg protein (mean +/- SEM). Among five of the nonsecreting pituitary adenomas examined, two had SRIH receptors with Kd values of 0.18 and 0.32 nM and Bmax values of 17.2 and 48.0 fmol/mg protein, respectively. In the remaining three, SRIH receptors were not detected. These results indicate that GH-secreting adenomas as well as some nonfunctioning adenomas have specific SRIH receptors, and hence, the function of the adenomas could be altered by SRIH.
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PMID:Specific somatostatin receptors on human pituitary adenoma cell membranes. 286 81

The influence of gamma-aminobutyric acid (GABA) on gastric somatostatin and gastrin release was studied using an isolated perfused rat stomach preparation. GABA dose-dependently inhibited somatostatin release (maximal inhibition of 44% at 10(-5)M GABA), whereas gastrin secretion was not affected. The GABA agonist muscimol led to a decrease in somatostatin release of similar magnitude. The GABA-induced changes were partially reversed by 10(-5)M atropine. Gastrin secretion was not influenced by either protocol. It is concluded that GABA as a putative neurotransmitter in the enteric nervous system is inhibitory to rat gastric somatostatin release in vitro via cholinergic pathways.
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PMID:Control of rat gastric somatostatin release by gamma-aminobutyric acid (GABA). 287 Sep 70

Addition of gamma-aminobutyric acid (GABA) to antral mucosal fragments in short-term incubation results in dose-dependent and bicuculline-sensitive stimulation of gastrin release and inhibition of somatostatin release, respectively. These effects of GABA on antral gastrin and somatostatin release closely resembled the actions of cholinergic agonists on G- and D-cell function. The present study examines the possibility that the effects of GABA on antral peptide release may be mediated, in part, through stimulation of antral cholinergic neurons. Inclusion of either atropine or pirenzepine in incubation medium prevented GABA-induced stimulation of gastrin release and inhibition of somatostatin release. Addition of the acetylcholinesterase inhibitor, physostigmine, caused a leftward shift in the GABA dose-response curve and increased by 10-fold the sensitivity of the antral preparation to GABA stimulation. Studies with tetrodotoxin suggest that GABA-stimulated gastrin release is mediated through activation of neurons contained within the antral mucosal/submucosal fragments. Hexamethonium, the ganglionic nicotinic receptor antagonist, did not affect GABA-induced gastrin release. These results indicate that GABA affects antral gastrin and somatostatin release through stimulation of antral postganglionic cholinergic neurons.
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PMID:Cholinergic mediation of gamma-aminobutyric acid-induced gastrin and somatostatin release from rat antrum. 287 17

Effects of cholecystokinin (CCK) and gastrin on the release of acetylcholine (ACh) and gamma-aminobutyric acid (GABA) were examined in the longitudinal muscle with myenteric plexus (LM-MP) preparations of the guinea pig small intestine. CCK and gastrin induced the Ca++-dependent and tetrodotoxin-sensitive release of [3H]ACh from the LM-MP preparations preloaded with [3H]choline. Proglumide, but not scopolamine, hexamethonium and [D-Pro2,D-Trp7,9]substance P inhibited the release of [3H]ACh induced by CCK and gastrin. The desensitization to CCK and gastrin was observed with a 30-min exposure of the preparation to CCK and gastrin, respectively, and the cross-desensitization to peptides was not observed, thereby indicating that these peptides induce the release of ACh mainly via respective receptors. Bicuculline which inhibited completely the release of [3H]ACh induced by GABA inhibited the release of [3H]ACh induced by CCK but not by gastrin by 42.3 +/- 4.22%. CCK, but not gastrin, produced the Ca++-dependent and tetrodotoxin-sensitive release of endogenous GABA and [3H]GABA from LM-MP preparations preloaded with [3H]GABA. The release of [3H]GABA induced by CCK was antagonized by proglumide, but not by scopolamine, hexamethonium and [D-Pro2,D-Trp7,9]substance P. These results provide evidence that the GABAergic neuron is stimulated by CCK, but not by gastrin and stimulates the cholinergic neuron.
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PMID:Cholecystokinin, but not gastrin, induces gamma-aminobutyric acid release from myenteric neurons of the guinea pig ileum. 291 83


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