Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatostatin is known to suppress various cellular functions of the gastrointestinal tract. In the present study, octreotide acetate, a synthetic long-acting somatostatin analogue was tested for its effects on some cellular functions of gastric mucosa. Octreotide raised the gastric mucosal pH within 1 h after a single subcutaneous injection to rats at doses of 1-100 microg/kg bodyweight. Serum gastrin levels increased transiently at a dose of 10 microg/kg bodyweight but not at 100 microg/kg. Basal levels of serum gastrin were not affected, while famotidine-induced gastrin secretion was suppressed by octreotide at a single dose of 100 microg/kg. The increase in the intragastric acidity and histidine decarboxylase activity following pentagastrin treatment was significantly reduced by octreotide. These results suggested that this somatostatin analogue inhibits the function of not only the parietal cell and G cell but also the enterochromaffin-like (ECL) cell, resulting in intraluminal hypoacidity.
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PMID:Acute in vivo effect of octreotide acetate, a somatostatin analogue on the cellular function of gastric mucosa in the rat. 1022 27

The present study investigated (1) the pharmacological profile of cholecystokinin (CCK) receptor subtypes involved in the regulation of gastric pepsinogen secretion, (2) the influence of gastric acidity on peptic responses induced by CCK-8-sulfate (CCK-8S) or gastrin-I; and (3) the mechanisms accounting for the effects of CCK-like peptides on pepsinogen secretion. In anaesthetized rats, i.v. injection of CCK-8S or gastrin-I increased both pepsinogen and acid secretion. The pepsigogue effect of CCK-8S was higher than that of gastrin-I, whereas acid hypersecretion after CCK-8S was lower than that induced by gastrin-I. Peptic output following CCK-8S was partly blocked by i.v. injection of the CCK1 receptor antagonist, devazepide (-75.3%), or the CCK2 receptor antagonist, L-365,260 [3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3 yl)-N'-(3-methyl-phenyl)urea; -27.9%], but was fully prevented by combined administration of devazepide and L-365,260. The gastric acid hypersecretory effect of CCK-8S was enhanced by devazepide (+84.5%) and blocked by L-365,260. In contrast, the gastric secretory actions of gastrin-I were insensitive to devazepide, but abolished by L-365,260. Excitatory effects of CCK-8S and gastrin-I were not modified by vagotomy or atropine, whereas cimetidine or alpha-fluoromethylhistidine (irreversible blocker of histidine decarboxylase) partly prevented acid hypersecretion induced by both peptides without affecting their pepsigogue effects. After pretreatment with omeprazole, both CCK-8S and gastrin-I failed to stimulate acid secretion, while they increased pepsinogen output. In rats with gastric perfusion of acid solutions, CCK-8S or gastrin-I increased peptic output in a pH-independent manner either with or without pretreatment with omeprazole. Ablation of capsaicin-sensitive sensory nerves as well as application of lidocaine to the gastric mucosa failed to modify the excitatory effects of CCK-8S or gastrin-I on pepsinogen and acid secretion. Blockade of the nitric oxide (NO) synthase pathway by N(G)-nitro-L-arginine-methyl ester prevented the pepsigogue actions of both CCK-8S and gastrin-I (-61.8% and -71.7%, respectively), without affecting the concomitant increase in acid output. In addition, both these peptides significantly increased the release of NO breakdown products into the gastric lumen. The present results suggest that: (1) both CCK1 and CCK2 receptors mediate the peptic secretory responses induced by CCK-like peptides; (2) the excitatory inputs of CCK-8S and gastrin-I to chief cells are not driven through acid-dependent mechanisms or capsaicin-sensitive afferent sensory nerves; and (3) under in vivo conditions, the stimulant actions of CCK-like peptides on pepsinogen secretion are mediated, at least in part, by an increase in NO generation.
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PMID:CCK1 and CCK2 receptors regulate gastric pepsinogen secretion. 1040 53

We have identified cotton rats with a high female-predominant occurrence of spontaneous gastric carcinomas localized to the oxyntic mucosa, classified as malignant enterochromaffin-like (ECL) omas. The present study was made to further characterize these ECLomas and surrounding oxyntic mucosa, both morphologically using histochemical and immunohistochemical methods, and for gene expression by northern blot analysis. Among eight female cotton rats, three had an irregularly thickened oxyntic mucosa, increased stomach weight and a high serum gastrin level. Histopathological examination showed adenomatous hyperplasia of the thickened oxyntic mucosa with areas of an invasive neoplastic tumour. Immunohistochemistry, using the general neuroendocrine cell marker chromogranin A (CgA) and the specific ECL cell marker histidine decarboxylase (HDC), showed a considerably increased ECL cell density. These ECL cells displayed active proliferation, with hyperplasia, dysplasia and neoplasia. Parietal cells were not found in the tumour tissue. Parietal cell density was only slightly reduced in the surrounding oxyntic mucosa. The antral mucosa was histopathologically normal with a normal number of gastrin-immunoreactive cells. Likewise, somatostatin-immunoreactive cells did not show any differences in the antral and oxyntic mucosa between rats with pathological and normal oxyntic mucosa. Northern blot analysis revealed increased expression of CgA and HDC mRNA in the thickened oxyntic mucosa, whereas H(+)/K(+) ATPase mRNA was similar in the oxyntic mucosa of those with thickened and normal oxyntic mucosa. Gastrin mRNA in the antral mucosa was high in animals with thickened oxyntic mucosa. Somatostatin mRNA expression was similar in the antral mucosa of control animals and animals with a thickened oxyntic mucosa. We conclude that the spontaneous gastric carcinoma occurring in female cotton rats is an ECLoma developing secondary to hypergastrinaemia due to reduced intragastric pH. The mechanism for reduced acidity is not known, but is not gastric atrophy.
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PMID:Spontaneous ECLomas in cotton rats (Sigmodon hispidus): tumours occurring in hypoacidic/hypergastrinaemic animals with normal parietal cells. 1060 29

This article summarizes data published during the past year that improve our understanding of the mechanisms by which various neurotransmitters, paracrine agents, and hormones regulate gastric acid secretion and are themselves regulated. The main stimulants of acid secretion are histamine, gastrin, and acetylcholine. The main inhibitor is somatostatin, which exerts a tonic restraint on parietal, enterochromaffin-like (ECL), and gastrin cells. Histamine, released from ECL cells, stimulates the parietal cell directly via H(2) receptors and indirectly via H(3) receptors coupled to inhibition of somatostatin secretion. Gastrin, acting via gastrin/cholecystokinin-B (CCK-B), now termed CCK(2), receptors on ECL cells activates histidine decarboxylase, releases histamine, and induces ECL hypertrophy and hyperplasia. The latter might be responsible for the rebound hyperacidity observed after withdrawal of long-term antisecretory therapy. The neurotransmitter pituitary adenylate cyclase-activating polypeptide stimulates histamine secretion from isolated ECL cells, but its physiologic role, if any, is not known. Acetylcholine, released from gastric postganglionic intramural neurons, stimulates the parietal cell directly via muscarinic M(3) receptors and indirectly by inhibiting somatostatin secretion. Although infection with H. pylori is associated with increased basal and stimulated acid outputs in patients with duodenal ulcer, most people infected with the organism are asymptomatic and have pangastritis with decreased acid output. In the latter, eradication of the bacterium leads to an increase in gastric acidity and is associated with a two-to threefold increase in gastroesophageal reflux.
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PMID:Gastric secretion. 1703 Nov 23

Amine production by amino acid decarboxylation is a common feature that is used by lactic acid bacteria (LAB) to complement lactic fermentation, since it is coupled with a proton-extruding antiport system which leads to both metabolic energy production and the attenuation of intracellular acidity. Analogous roles are played in LAB by both malolactic fermentation (MLF) and the arginine deiminase (ADI) pathway. The present investigation was aimed at establishing reciprocal interactions between amino acid decarboxylation and the two above mentioned routes. The analyses were carried out on a Lactobacillus hilgardii strain (ISE 5211) that is able to decarboxylate histidine to histamine, which had previously been isolated from wine and whose complete genome is still unknown. The 2DE proteomic approach, followed by MALDI TOF-TOF and De Novo Sequencing, was used to study the protein expression levels. The experimental evidence has indicated that malate does not influence histidine decarboxylase (HDC) biosynthesis and that histidine does not affect the malolactic enzyme level. However, the expression of the ADI route enzymes, arginine deiminase and ornithine transcarbamylase, is down-regulated by histidine: this biosynthetic repression is more important (4-fold) in cultures that are not supplemented with arginine, but is also significant (2-fold) in an arginine supplemented medium that normally induces the ADI pathway. On the other hand, arginine partially represses HDC expression, but only when histidine and arginine are both present in the culture medium. This proteomic study has also pointed out a down-regulation exerted by histidine over sugar metabolism enzymes and a GroEL stress protein. These data, together with the reciprocal antagonism between arginine deimination and histidine decarboxylation, offer clue keys to the understanding of the accumulation of lactate, amine, ammonia and ethylcarbamate in wine, with consequent implications on different health risk controls.
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PMID:ADI pathway and histidine decarboxylation are reciprocally regulated in Lactobacillus hilgardii ISE 5211: proteomic evidence. 2097 11