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)

Cysteamine and propionitrile are members of a family of compounds which induce the formation of acute duodenal ulcers in fasted and fed rats. Gastric acid secretion is increased by both agents, and acid hypersecretion appears to be required for ulcer formation. To determine the role of gastrin in the ulcerogenic mechanism, cysteamine and propionitrile were administered to fasted rats and their effect on fasting and food-stimulated serum gastrin levels was studied. Intragastric administration of cysteamine caused a 3- to 4-fold increase in fasting serum gastrin levels over the values of controls. Propionitrile was a less effective stimulant of gastrin release, causing a 1.5- to 2-fold increase in gastrin levels over matched control rats. The food-stimulated rise in serum gastrin levels after either a chow meal or intragastric instillation of a peptone solution was markedly enhanced by cysteamine pretreatment. Three hours after feeding the serum gastrin levels of cysteamine pretreated rats were 6 times higher than those of fed controls. The high serum gastrin levels of cysteamine-pretreated fed rats could not be explained solely by the additive effects of cysteamine and food, indicating that a potentiating interaction may exist between the two stimulants of gastrin release. The importance of this drug-induced stimulation of gastrin release, under both fasted and fed conditions, in the ulcerogenic process has yet to be ascertained.
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PMID:Duodenal ulcerogens, cysteamine and propionitrile, stimulate serum gastrin levels in the rat. 91 72

Cysteamine, a potent duodenal ulcerogen, stimulates gastric acid and gastrin secretion and decreases immunoreactive somatostatin (IRS) from the gut and hypothalamus of the rat. To elucidate the structural requirements for this effect, we tested a series of cysteamine analogs for their IRS decreasing activity in comparison with their nucleophilic and reducing potencies. Adult female rats were sacrificed 4 hr after p.o. administration of the test chemicals given in molar equivalents to 30 mg/100 g of cysteamine-HCl. IRS decreasing activity in gastric mucosa, expressed as percentage of controls is listed in descending order: cystamine (55%), cysteamine (59%), 2-dimethylaminethanethiol (59%), ethylamine (66%), 1,3-propanedithiol (70%), propylamine (75%) and 3-aminothiophenol (79%). The following thiols and amines had no IRS decreasing effect (80% of controls): L-cysteine, ethanethiol, 1-propanethiol, penicillamine, dimercaprol, 1-4-dithiothreitol, ethanolamine, propionitrile, n-butyronitrile, o-, m- or p-aminophenol. The aryl 2-, 3- or 4-aminothiophenols, unlike most of their aminophenol analogs also decreased immunoreactive prolactin in the pituitary by 38 to 78%. IRS decreasing activity was independent of the reducing potency of cysteamine derivatives but was correlated significantly (r = 0.793, P < .01) with electron affinity of -SH, -NH2, -OH and -CN radicals in terminal alkyl chemicals. The structural requirement for decreasing activity is the presence of either -SH and -NH2 on a 2 to 3 carbon alkyl or aryl molecule. Both radicals when present together increase potency.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Somatostatin depleting potency of cysteamine-related thiols and amines in the rat: structure-activity relation. 135 14

Single subcutaneous administration of cysteamine (2-aminoethanethiol, CSH) produces duodenal ulceration in rats within 24 h. Depletion of circulating and tissue somatostatin (SOM), hypergastrinemia and gastric acid hypersecretion have all been postulated as the pathophysiological response to CSH leading to ulceration. The purpose of this study was to analyze the synthesis, storage and secretion of gastrin and SOM as well as structural changes in SOM peptide after CSH treatment. Injection of 300 mg/kg (s.c.) of CSH caused macroscopic duodenal ulcers in seven out of eight rats at 24 h. Hypergastrinemia was seen within 30 min (from 23 +/- 4 to 74 +/- 20 pmol/l), and persisted for 4 h. Antral gastrin content was elevated at 30 min (2539 +/- 114 pmol/g) when compared to saline controls (1589 +/- 101 pmol/g). Plasma SOM did not change over the 24 h but antral SOM increased at 30 min (from 120 +/- 3 to 230 +/- 23 pmol/g) and remained elevated at 2 h (374 +/- 48 pmol/g) and 4 h (357 +/- 37 pmol/g). Fundic and duodenal SOM followed a similar pattern. Antral SOM mRNA was also elevated over the first 4 h (3-fold increase, P less than 0.05). HPLC analysis of antral tissue extracts revealed the presence of additional molecular forms of SOM which, however, differed from the major products of in vitro reduction with either CSH or dithiothreitol. Thus, the in vivo effect of CSH on SOM cannot be solely explained by a reductive opening of the disulphide bond. These results suggest that duodenal ulceration in rats treated with CSH is not related in a simple fashion to depletion of immunoreactive SOM. Early induction of hypergastrinemia may be important in the onset of ulceration. The value of CSH as a SOM depleting tool in gastrointestinal tissue must remain in doubt.
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PMID:Cysteamine can induce duodenal ulceration in rats without depletion of immunoreactive somatostatin. 168 22

To determine whether cholecystokinin secretion is regulated by endogenous somatostatin, somatostatin deficiency was induced in vivo with cysteamine (250 mg/kg body wt, IV) or anti-somatostatin antiserum in anaesthetized rats and in vitro with cysteamine (30 micrograms/mL) in a rat duodenum-incubation system. Cholecystokinin secretion was assessed in vivo by measuring amylase in duodenal perfusates collected at 10-minute intervals for 1 hour and in vitro by a carboxy-terminal radioimmunoassay. Cysteamine induced a marked decrease in duodenal immunoreactive somatostatin both in vivo (50%) and in vitro (60%). The rate of amylase secretion increased from 9.7 +/- 2.1 U (mean +/- SE) to 28.0 +/- 4.8 U at 20 minutes (P less than 0.001). The cholecystokinin-receptor antagonist CR-1392 abolished amylase response for 30 minutes, whereas the more potent antagonists Asperlicin (18.0 mg/kg body wt, IV) and L-364,718 (0.25 mg/kg body wt, IV) caused prolonged blockade. The rate of amylase secretion in gastrectomized animals increased from 7.2 +/- 2.0 U to 15.0 +/- 2.2 U 20 minutes after cysteamine administration (P less than 0.01), indicating that the effect was not due to the presence of gastrin. In vitro, cysteamine caused a nearly fourfold increase in cholecystokinin secretion compared with controls (63.1 +/- 4.9 vs. 15.2 +/- 3.7, respectively; P less than 0.001). In vivo immunoneutralization of circulating somatostatin with a high-affinity and high-capacity antiserum produced no significant change in the rate of amylase secretion. These results suggest that cholecystokinin secretion is tonically inhibited by somatostatin and that this effect is mediated by locally secreted (paracrine) but not by circulating somatostatin.
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PMID:Cysteamine induces cholecystokinin release from the duodenum. Evidence for somatostatin as an inhibitory paracrine regulator of cholecystokinin secretion in the rat. 169 33

The effect of oral administration of cysteamine (2-aminoethanethiol hydrochloride) on the incidence and histology of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was investigated in inbred Wistar rats. Oral administration of 0.4% cysteamine in food after treatment with MNNG for 25 weeks significantly reduced the incidence and number of adenocarcinomas of the glandular stomach in experimental Week 52. Histological examination showed that adenocarcinomas that did develop in rats fed on cysteamine had high mucin-producing activity. Furthermore, oral administration of cysteamine caused a significant increase in serum gastrin level and significant decreases in the antral mucosal pH and the labeling indices of the antral mucosa. These findings indicate that cysteamine inhibits the development of gastric adenocarcinomas when given orally. This effect may be related to its ability to decrease proliferation of antral mucosal cells.
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PMID:Protective effect of oral cysteamine against induction of gastric cancer by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. 292 Jul 71

The effects of propranolol and cimetidine on inhibition by cysteamine (2-aminoethanethiol hydrochloride) of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and on gastric acid secretion, serum gastrin level, and labelling index of the gastric mucosa were investigated in inbred Wistar rats. Rats received alternate-day injections of cysteamine (25 mg/kg body weight) with or without propranolol (dl-propranolol hydrochloride) (2 mg/kg bw) or cimetidine (50 mg/kg bw) in depot form after 25 weeks of oral treatment with MNNG. Prolonged administration of cysteamine significantly reduced the incidence of adenocarcinoma of the glandular stomach. A combination of cysteamine and propranolol significantly accelerated the inhibitory effect of cysteamine on gastric carcinogenesis. However, with concomitant administration of cysteamine and cimetidine, the incidence of adenocarcinoma was slightly but not significantly increased as compared to that after treatment with cysteamine alone. Administration of cysteamine caused a significant increase in gastric acid secretion and serum gastrin level, and a significant decrease in the labelling index of the antral mucosa. A combination of cysteamine and propranolol significantly increased gastric acid secretion by cysteamine alone and significantly decreased the labelling index of the antral mucosa. With this treatment, the serum gastrin level was significantly higher than the basal level, but the stimulated serum gastrin level was significantly lower than observed that after administration of cysteamine alone. In contrast, concomitant administration of cysteamine and cimetidine caused a significant decrease in gastric acid secretion and significant increase in the serum gastrin level as compared to the levels seen after treatment with cysteamine alone, but had no influence on the labelling index of the antral mucosa. These findings indicate that hypersecretion of acid, but not hypergastrinemia associated with hyposecretion of acid or achlorhydria, exerts a protective effect against gastric carcinogenesis, and that this effect may be related to its activity in decreasing proliferation of the antral mucosa.
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PMID:Effects of propranolol and cimetidine on cysteamine inhibition of gastric carcinogenesis induced in Wistar rats by N-methyl-N'-nitro-N-nitrosoguanidine. 292 76

Cysteamine-induced duodenal ulceration in rats is accompanied by increased circulating gastrin. Although cysteamine appears to exert a direct action on the gastrin cell some groups have provided evidence for an involvement of the autonomic nervous system. The current experiments were performed to determine whether beta-adrenergic or cholinergic (muscarinic) pathways are involved in the acute effect of cysteamine on gastrin secretion in the isolated perfused rat stomach. Cysteamine (1 mM) increased gastrin (IRG) secretion to a maximum ranging between 100% and 192% above basal. A cysteamine concentration of 5mM resulted in peak levels ranging between 150% and 1050% above basal. Addition of atropine or propranalol did not influence the responses obtained. The present results, therefore, do not support a role for either cholinergic or beta-adrenergic pathways in cysteamine-induced gastrin release at the level of the stomach and suggest that in vivo such autonomic effects are mediated extrinsically.
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PMID:The effect of muscarinic and beta-adrenergic blockade on cysteamine-induced gastrin secretion by the isolated perfused rat stomach. 304 Nov 47

The effect of cysteamine (2-aminoethanethiol hydrochloride) on the incidence and histology of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was investigated in inbred Wistar rats. Prolonged administration of 25 or 50 mg per kg body weight of cysteamine after treatment with MNNG for 25 weeks significantly reduced the incidence and number of adenocarcinomas of the glandular stomach. Histological examination showed that the adenocarcinomas that did develop in rats treated with these 2 doses of cysteamine had high mucin-producing activity. Furthermore, treatment with cysteamine caused significant increases in serum gastrin level and gastric acid secretion, together with significant decreases in the antral mucosal pH and the labelling indices of pyloric and oxyntic gland mucosae and gastric cancer. These findings indicate that cysteamine inhibits the development of gastric adenocarcinomas and that its effect may be related to decreasing proliferation of cells in the gastric mucosae.
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PMID:Inhibitory effect of prolonged administration of cysteamine on experimental carcinogenesis in rat stomach induced by N-methyl-N'-nitro-N-nitrosoguanidine. 334 7

Cysteamine (beta-mercaptoethylamine HCl) administration to rats induces a hypergastrinemia and a reduction in gastric tissue somatostatin content. The possibility that this reduction may contribute to the elevated gastrin levels has been investigated in the isolated perfused rat stomach. Cysteamine (1 mM) rapidly increased immunoreactive gastrin release to levels ranging between 41% and 125% above basal. Increasing the dose to 10 mM caused a 1148% increase in immunoreactive gastrin. Secretion of somatostatinlike immunoreactivity did not change. Perfusion of gastric inhibitory polypeptide (1 nM) induced a sustained increase in somatostatinlike immunoreactivity secretion and a transient rise in gastrin. Addition of 10 mM cysteamine during gastric inhibitory polypeptide perfusion caused a 300% increase in immunoreactive gastrin. These levels were lower than in response to cysteamine alone. The results demonstrate that cysteamine can stimulate immunoreactive gastrin secretion without any change in somatostatinlike immunoreactivity release. When somatostatinlike immunoreactivity secretion is stimulated by an agent such as gastric inhibitory polypeptide, the cysteamine-induced release of immunoreactive gastrin is attenuated, suggesting the presence of a functional linkage between somatostatin and gastrin under these conditions.
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PMID:Effect of cysteamine on secretion of gastrin and somatostatin from the rat stomach. 614 43

Cysteamine administration is followed by stomach and duodenal ulcers in rats. We aimed to establish a time relationship between changes in gastric mucosal histamine, histamine formation capacity (HFC) and plasma gastrin after cysteamine administration. Up to 4 h after cysteamine s.c., no ulcers were found. Plasma gastrin rose after cysteamine and was higher than in controls 2h after injection. Mucosal histamine fell after 4h; no other significant changes were found in mucosal histamine and HFC. A direct correlation was found between plasma gastrin and HFC in both controls and after cysteamine. It is suggested that the changes indicate that cysteamine releases gastrin, which increases HFC and thus histamine. The fall in histamine seems to indicate utilization of histamine in acid production.
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PMID:Gastric mucosal histamine, histamine formation capacity (HFC) and plasma gastrin after cysteamine administration. 649 88


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