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

Acid-sensing pathways, which trigger mucosal defense mechanisms in response to luminal acid, involve the rapid afferent-mediated "capsaicin pathway" and the sustained "prostaglandin (PG) pathway." Luminal acid quickly increases protective PG synthesis and release from epithelia, although the mechanism by which luminal acid induces PG synthesis is still mostly unknown. Acid exposure augments purinergic ATP-P2Y signaling by inhibition of intestinal alkaline phosphatase activity. Since P2Y activation increases intracellular Ca2+, we further hypothesized that ATP-P2Y signals increase the generation of H2O2 derived from dual oxidase, a member of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family activated by Ca2+. Our recent studies suggest that acid exposure increases H2O2 output, followed by phospholipase A2 and cyclooxygenase activation, increasing PG synthesis. Released prostaglandin E2 augments protective HCO3- and mucus secretion via EP4 receptor activation. Thus, the PG pathway as a component of duodenal acid sensing consists of acid-related intestinal alkaline phosphatase inhibition, ATP-P2Y signals, dual oxidase 2-derived H2O2 production, phospholipase A2 activation, prostaglandin E2 synthesis, and EP4 receptor activation. The PG pathway is also involved in luminal bacterial sensing in the duodenum via activation of pattern recognition receptors, including Toll-like receptors and nucleotide-binding oligomerization domain 2. The presence of acute mucosal responses to luminal bacteria suggests that the duodenum is important for host defenses and may reduce bacterial loading to the hindgut using H2O2, complementing gastric acidity and anti-bacterial bile acids.
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PMID:Prostaglandin pathways in duodenal chemosensing. 2552 40

Gastric acid is of paramount importance for digestion and protection from pathogens but, at the same time, is a threat to the integrity of the mucosa in the upper gastrointestinal tract and may give rise to pain if inflammation or ulceration ensues. Luminal acidity in the colon is determined by lactate production and microbial transformation of carbohydrates to short chain fatty acids as well as formation of ammonia. The pH in the oesophagus, stomach and intestine is surveyed by a network of acid sensors among which acid-sensing ion channels (ASICs) and acid-sensitive members of transient receptor potential ion channels take a special place. In the gut, ASICs (ASIC1, ASIC2, ASIC3) are primarily expressed by the peripheral axons of vagal and spinal afferent neurons and are responsible for distinct proton-gated currents in these neurons. ASICs survey moderate decreases in extracellular pH and through these properties contribute to a protective blood flow increase in the face of mucosal acid challenge. Importantly, experimental studies provide increasing evidence that ASICs contribute to gastric acid hypersensitivity and pain under conditions of gastritis and peptic ulceration but also participate in colonic hypersensitivity to mechanical stimuli (distension) under conditions of irritation that are not necessarily associated with overt inflammation. These functional implications and their upregulation by inflammatory and non-inflammatory pathologies make ASICs potential targets to manage visceral hypersensitivity and pain associated with functional gastrointestinal disorders. This article is part of the Special Issue entitled 'Acid-Sensing Ion Channels in the Nervous System'.
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PMID:Acid-sensing ion channels in gastrointestinal function. 2558 94

Luminal bacteria, one of the main aggressive factors of nonsteroidal anti-inflammatory drugs (NSAIDs), induce small intestinal mucosal injury. Because most bacteria invading from the mouth are eliminated by the highly acidic gastric environment, the upper small intestine contains relatively low numbers of microorganisms. With decreased peristalsis, decreased acidity, and lower oxidation-reduction potential, the ileum maintains a more diverse microflora and a higher bacterial population. As NSAID-induced small intestinal ulcerations tend to localize in the small intestinal distal part, as viewed by capsule endoscopy, the ulcers are in contact with a large amount of luminal bacteria. Recently, it was reported that proton-pump inhibitors (PPIs) exacerbate NSAID-induced small intestinal injury in rats. The study showed that PPIs impair the ability to disinfect due to the PPI-induced low acidic gastric environment, and this resulted in transubstantiation of intestinal flora which exacerbated NSAID-induced small intestinal injury. If it is true that PPIs exacerbate small intestinal injury, the methods of preventing NSAID-induced gastroduodenal injury to defend PPI-induced small intestinal injury should be reconsidered. Following several studies, there may be a possibility that probiotics and prebiotics are useful treatments for the prevention of NSAID-induced small intestinal injury. A method of determining bacterial flora maintenance including alteration of the environment and the administration of various drugs is required.
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PMID:Latest concepts on the association between nonsteroidal anti-inflammatory drug-induced small intestinal injury and intestinal bacterial flora. 2618 29


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