Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vagal afferents are extensively distributed in the digestive tract from the oesophagus to the colon. They are involved in the reflex control of normal gastrointestinal (GI) tract function (e.g. secretion and motility) as well as reflexes more characteristic of diseases such as functional dyspepsia and gastroesophageal reflux disease (e.g. vomiting, disordered lower esophageal sphincter relaxation and gastric accommodation). They are also implicated in signalling non-painful sensations (e.g. nausea and early satiety) associated with disease. A variety of receptors has been identified on vagal afferents, which can either enhance (e.g. 5-HT3, CCK1, VR1 and NK1 receptors) or reduce (e.g. ghrelin, leptin, k-opioid and GABAB receptors) activity, offering a range of potential therapeutic targets. Commonly used laboratory species (e.g. rat and mouse) lack an emetic reflex, and the implications of this for models of upper GI disorders have been explored in the light of expanding knowledge of the neuropharmacology of the emetic reflex implicating glutamate, prostanoids, cannabinoids and substance P. Additional pathophysiological roles for vagal afferents (e.g. in thermoregulation, arousal and fatigue) are being investigated, raising the intriguing possibility of the vagus as a target in non-GI disorders.
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PMID:Abdominal vagal afferent neurones: an important target for the treatment of gastrointestinal dysfunction. 1248 26

The therapeutic actions of cannabinoids have been known for centuries. In the last 25 years this area of research has grown exponentially with the discovery of specific cannabinoid receptors and endogenous ligands. In the enteric nervous system of gastrointestinal tract, cannabinoid receptors are located on enteric nerve terminals where they exert inhibitory actions on neurotransmission to reduce motility and secretion. Endogenous cannabinoids are present in the enteric nervous system, as are the degradative enzymes necessary to inhibit their action. The cellular mechanism of action of endocannabinoids has not been established in the enteric nervous system. Endocannabinoids not only act at cannabinoid receptors, but potentially also at vanilloid and 5-HT3 receptors, both of which are expressed in the gastrointestinal tract. The interactions between endocannabinoids and these other important receptor systems have not been extensively investigated. A greater understanding of the endocannabinoid system in the enteric nervous system could lead to advances with important therapeutic potential in the treatment of gastrointestinal disorders such as irritable bowel syndrome, inflammatory bowel disease, secretory diarrhoea and gastro-oesophageal reflux disease.
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PMID:Review article: endocannabinoids and their receptors in the enteric nervous system. 1619 88

Dynogen Pharmaceuticals Inc, under license from Mitsubishi Pharma Corp, is developing pumosetrag (MKC-733, DDP-733), an orally available gastroprokinetic agent and locally acting 5-HT3 partial agonist, for the potential treatment of irritable bowel syndrome (IBS) with constipation and nocturnal gastroesophageal reflux disease (GERD). In September 2005, Dynogen commenced a phase II proof-of-concept trial of pumosetrag in IBS with constipation; positive results were reported in February 2007 and a phase IIb trial was to start in the fourth quarter of 2007. In September 2006, the company had initiated a phase Ib trial in nocturnal GERD.
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PMID:Drug evaluation: Pumosetrag for the treatment of irritable bowel syndrome and gastroesophageal reflux disease. 1752 Aug 71

Traditional Japanese medicine (Kampo) is used to treat various disorders of the gastrointestinal tract in Japan, where it is fully integrated into the modern healthcare system. Recently, scientific research on herbal medicine in Japan has been reported in English journals. The objective of the current review is to introduce two traditional Japanese medicines and to provide evidenced-based information regarding their use. Daikenchuto, which consists of three different herbs, is the most frequently prescribed traditional Japanese medicine in Japan. Daikenchuto stimulates gastrointestinal motility though a neural reflex involving presynaptic cholinergic and 5-HT3 receptors. Daikenchuto improves postoperative bowel motility and postoperative ileus. Furthermore, it is reported to cause an increase in gastrointestinal hormones (motilin, vasoactive intestinal peptide, and calcitonin gene-related peptide) and intestinal blood flow. Rikkunshito, a traditional Japanese medicine consisting of eight herbs, is thought to stimulate gastrointestinal motility and ghrelin secretion. Rikkunshito is effective for improving the symptoms of functional dyspepsia, gastroesophageal reflux disease, and cisplatin-induced anorexia and vomiting. Traditional Japanese medicine has the potential to be used successfully in the treatment of gastrointestinal disorders. Details regarding the physiological and clinical effects of traditional Japanese medicine must be further examined in order to become more widely accepted in other countries.
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PMID:The effect of traditional Japanese medicine (Kampo) on gastrointestinal function. 2111 Jan 52