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)

Endogenous prostaglandin and mucus have been recognized as important protective factors in the gastric mucosa. However, the regulatory mechanisms of these agents have not been well studied. The aim of the present study was to investigate the effects of acid secretagogues on cyclic adenosine monophosphate (cAMP) formation, prostaglandin E2 (PGE2) production, and mucus secretion by isolated parietal cells and culture mucous cells from adult rabbits. Rabbit parietal cells were enriched by nonlinear Percoll gradients after the isolation of rabbit gastric mucosal cells with collagenase and ethylenediaminetetraacetic acid (EDTA). Rabbit gastric mucous cells were cultured in 10% fetal bovine serum added to Ham's F12 medium. As gastric acid secretagogues, histamine, carbachol, gastrin, and 2-chloroadenosine were tested. To evaluate the effects of the second messengers of cellular signal transduction on protective agents, A23187, which is a calcium ionophore, and cAMP were used. PGE2 and cAMP were measured by radioimmunoassay. The release of [3H]glucosamine from prelabeled cells was used as an indicator of mucus secretion. Histamine, carbachol, gastrin, and 2-chloroadenosine did not modulate PGE2 production by parietal cells. Exogenously administered cAMP did not affect PGE2 production by parietal cells, whereas it was significantly increased by A23187. 2-Chloroadenosine but not histamine or carbachol significantly increased cAMP formation by mucous cells. Histamine, carbachol, and gastrin did not have significant effects on PGE2 production by mucous cells. 2-Chloroadenosine, which increased cAMP, also did not modulate PGE2 production. A23187 but not cAMP increased PGE2 production by mucous cells. None of the acid secretagogues used in the present study modulated mucus secretion. A23187 but not cAMP significantly increased mucus secretion by cultured mucus cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of acid secretagogues on protective agents of gastric cells from adult rabbits in vitro. 132 Nov 82

The role of neuropeptides in the regulation of macromolecule secretion from human nasal mucosa is incompletely understood. Previous in vitro explant culture studies have demonstrated the effects of neuropeptides on lactoferrin release from serous cells and 3H-glucosamine labeled respiratory glycoconjugate secretion from mucus-containing cells. The generation of a new monoclonal antibody, 7F10, has led to the development of an ELISA for high molecular weight respiratory mucous glycoproteins (MGP). This ELISA was used to measure the ability of sensory, parasympathetic and sympathetic neuropeptides to stimulate MGP release from human nasal mucosal fragments in short term explant culture in vitro. Significant MGP release was stimulated by the sensory neuropeptides gastrin releasing peptide (10 microM GRP: 10.6% +/- 2.4% increase, n = 8, P less than 0.01 vs. control), substance P (1 microM SP: 12.5% +/- 5.4%, n = 11, P less than 0.05), neurokinin A (1 microM NKA: 17.8 +/- 4.3%, n = 6, P less than 0.01), while calcitonin gene related peptide (CGRP) was without effect. Vasoactive intestinal peptide (VIP), a neurotransmitter from parasympathetic nerves, induced significant dose dependent MGP secretion, but had no additive or inhibitory interaction with methacholine-induced secretion. Neuropeptide Y (NPY), present in sympathetic nerves, had no effect on MGP secretion. These observations correlate with the effects of neuropeptides on serous cell lactoferrin secretion, and the presence of specific GRP, SP, and VIP binding sites on human nasal submucosal glands that have been detected by autoradiography. GRP and tachykinins (SP and NKA) from sensory nerves, and VIP released during parasympathetic reflexes may significantly stimulate mucous and serous cell secretion from human nasal mucosa in vivo.
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PMID:The effects of neuropeptides on mucous glycoprotein secretion from human nasal mucosa in vitro. 138 97

1. A suspension of cells, containing about 30% mucous cells, was isolated from the rat fundic mucosa, and was pre-incubated with D-[6-3H]glucosamine. 3H-labelled material subsequently released into the medium was separated by Fast Protein Liquid Chromatography on a Superose 6 column. 2. A sharp peak of labelled high molecular weight material eluted from the column close to the void volume. This material was identified as mucous glycoprotein by its similar chromatographic behaviour to partially purified rat gastric mucous glycoprotein, by its resistance to complete degradation by papain and by its behaviour on treatment with dithiothreitol. On a caesium chloride density gradient the labelled material was virtually all located between densities of 1.35 and 1.53 g/ml. with the main peak at 1.40 g/ml. 3. A broad peak of lower molecular weight material was also eluted from the column. The release of this unidentified material did not seem to be closely associated with the release of mucous glycoprotein from the cells. 4. Release of mucous glycoprotein was stimulated by secretin (half-maximally effective concentration 2.3 nM, 84% stimulation above basal release at 100 nM), and by isoprenaline (half-maximally effective concentration 34 nM, 33% stimulation at 1 microM). Carbachol (0.5 nM) produced a significant (18-29%) stimulation of mucus secretion, but gastrin (100 nM), histamine (0.5 mM) and epidermal growth factor (200 nM) were without effect. 5. The preparation should prove useful in the identification of the agents which regulate gastric mucus secretion.
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PMID:Regulation of mucus secretion by cells isolated from the rat gastric mucosa. 238 55

N,N-Dimethyl-N'-(2-diisopropylaminoethyl)-N-(4,6-dimethyl-2-pyridyl)urea (L-634,366) was selected from a series of pyridylurea compounds with antisecretory activity as a potential therapeutic agent for the treatment of ulcer disease. L-634,366 was an effective inhibitor of gastric secretion evoked by gastrin, histamine and 2-desoxy-D-glucose (2-DG) in conscious dogs. Orally, L-634,366 was slightly less potent than the reference H2 receptor blocker, cimetidine as an inhibitor of secretion evoked by histamine, but was equipotent as an inhibitor of secretion evoked by gastrin and 2-DG. In vitro L-634,366 was a weak antagonist of histamine (H2) receptor responses in the guinea-pig atria and rat uterus; in the atria the antagonism appeared to be noncompetitive. In the anesthetized dog, L-634,366 possessed weak anticholinergic activity as compared to atropine in reducing vagally mediated cardiovascular, antral motor responses and with regard to antagonizing the pressor response to the muscarinic stimulant, McN 343-A. The anticholinergic activity of L-634,366 was lower and more selective than that of pirenzepine or atropine in producing mydriasis in mice, in antagonizing acetylcholine induced bradycardia in guinea-pig atria, methacholine and acetylcholine elicited contractions in the guinea-pig ileum and QNB binding to muscarinic receptors. L-634,366, like carbenoxolone, increased incorporation of 3H-glucosamine in gastric mucous indicating an increase in synthesis or turnover of mucous. L-634,366 is a novel compound possessing a broad spectrum of antisecretory activity; in vitro studies suggested a weak noncompetitive inhibition of the histamine-H2 receptor in atria.
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PMID:Gastric antisecretory and pharmacologic properties of N,N-dimethyl-N'-(2-diisopropylaminoethyl)-N-(4,6-dimethyl-2-pyridyl)ur ea (L-634,366). 287 93

We examined the effects of the gastrin family of peptides on gastric mucus glycoprotein (mucin) biosynthesis in rat gastric mucosa using an organ culture technique. Radiolabeled mucin was obtained from the tissue and culture medium of the corpus and antrum of rat stomach incubated for 5 hr with [3H]glucosamine (GlcN), [14C]threonine (Thr), and [35S]sulfate in vitro. With the addition of 10(-8) and 10(-7) M tetragastrin to the culture medium, [3H]GlcN labeled mucin in the corpus tissue increased to 120-135% that of the control (P < 0.01). The biosynthetic responses to cholecystokinin (CCK)-8 and the 17-peptide gastrin were essentially the same as that to tetragastrin. Tetragastrin 10(-8) M also increased the incorporation of [35S]sulfate into the corpus mucin but failed to change [14C]Thr incorporation. In the antrum, biosynthetic activity showed no significant change with 10(-9) approximately 10(-5) M tetragastrin. Ranitidine, diphenhydramine and omeprazole at 10(-5) M did not suppress the tetragastrin-induced increase in [3H]GlcN incorporation into mucin, but L-365,260 at a concentration of 10(-6) M completely blocked this effect. These results suggest that gastrin stimulates mucin production via CCK-B/gastrin receptors in the oxyntic region of rat gastric mucosa.
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PMID:Stimulation of mucus glycoprotein biosynthesis in rat gastric mucosa by gastrin. 824 Apr 10

Although gastrin, histamine, and carbachol (CCh) accelerate gastric mucin metabolism, information about their target cells of mucin production is lacking. To clarify this, we examined the effects of these stimulants, including the possible participation of nitric oxide (NO), on mucin biosynthesis in distinct sites and layers of rat gastric mucosa. Pieces of tissue obtained from the corpus and antrum were incubated in a medium containing radioactive precursors and each stimulant, with or without NO synthase (NOS) inhibitor. Distribution of NOS was compared with that of the specific mucins by immunostaining using specific antiserum and monoclonal antibodies. In the full-thickness corpus mucosa, tetragastrin enhanced [3H]glucosamine incorporation into mucin but had no effect on [14C]threonine incorporation. Both histamine and CCh dose dependently increased 3H- and 14C-labeled corpus mucin. Only CCh stimulated antral mucin biosynthesis. CCh stimulation was noted in the corpus mucosa after removal of surface mucous cells, but stimulation by tetragastrin or histamine disappeared as a result of this pretreatment. Only tetragastrin-induced activation was completely blocked by the NOS inhibitor. NOS immunoreactivity was limited to surface mucous cells. Mucus-producing cells present in the different sites and layers of the gastric mucosa have distinct mechanisms for regulation of mucin biosynthesis. Gastrin-stimulated mucin biosynthesis mediated by NO is limited to surface mucous cells of rat gastric oxyntic mucosa.
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PMID:Distinct effects of tetragastrin, histamine, and CCh on rat gastric mucin synthesis and contribution of NO. 945 83

Mucin biosynthesis is stimulated by gastrin during the process of glycosylation in the corpus mucosa of the rat stomach. The purpose of this study was to clarify, using an organ culture technique, whether biosynthetic responses to histamine in the rat gastric mucin are the same as that to gastrin. Radiolabeled mucin was obtained from the corpus and antral mucosa of the rat stomach after in vitro incubation for 5 h with [3H]glucosamine (GlcN), [14C]threonine (Thr), and [35S]sulfate. Addition of histamine (10(-7)-10(-5) M) to the culture medium increased [3H]GlcN-labeled mucin in the corpus tissue in a concentration-dependent manner. In the antrum, there was no significant change in the biosynthetic activity of mucin in response to histamine. Histamine at 10(-5) M also increased the incorporation of both [35S]sulfate and [14C]Thr into the corpus mucin. These results indicate that histamine stimulates the biosynthesis of the mucin peptide, as well as the glycosylation step in the corpus, and suggest that the effect of histamine on mucin synthesis is distinct from that of gastrin.
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PMID:Effects of histamine on mucin biosynthesis in rat gastric mucosa. 947 32

The effects of tetragastrin on gastric mucin biosynthesis in middle-aged rats were compared with those in young rats. The incorporation of [3H]glucosamine and [35S]sulfate into mucin was stimulated by tetragastrin in cultured corpus mucosa from 7-week-old rats. In contrast, tetragastrin could not enhance mucin biosynthesis in stomachs from 52-week-old rats. The isosorbide dinitrate-induced stimulation of corpus mucin biosynthesis observed in middle-aged rats was essentially the same as that seen in young rats. Nitric oxide (NO) synthase activity of the corpus was significantly reduced in the middle-aged rats compared to the young rats. NO synthase-immunoreactivity was observed at surface mucous cells in the corpus mucosa of young, but not of middle-aged, rats. These results suggest that aging decreases the effect of gastrin on gastric mucin biosynthesis through the age-related loss of NO synthase function in the surface mucous cell layer of rat stomach.
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PMID:Age-related stimulation by tetragastrin of gastric mucin biosynthesis in rat. 1006 56