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)

Purinergic receptors are implicated in nociceptive signaling in small primary afferents via activation of adenosine triphosphate (ATP). ATP appears to mediate HCl-induced transient receptor potential vanilloid receptor 1 (TRPV1) activation in esophageal mucosa. Up-regulation of TRPV1 expression in gastroesophageal reflux disease (GERD) is associated with increased nerve growth factor (NGF) and glial derived neurotrophic factor (GDNF). This study aims to genetically determine the expression of purinergic receptors in severe inflamed human esophagus. Distal esophageal biopsies from the subjects with erosive GERD, asymptomatic patients (AP) and healthy ones were examined. Using real-time qPCR for detecting purinergic receptors (P2X2, P2X3, P2X7, P2Y1, P2Y2, P2Y4, P2Y6 and P2Y12), TRPV1, TRPV4, NGF, and GDNF was done in this study. Both P2X3 and P2X7 mRNA expressions in GERD patients significantly increased than those in healthy controls (P < 0.001) and AP (P < 0.001), but P2X2, P2Y1, P2Y2, P2Y4, P2Y6, P2Y12 or P2Y12 had no difference within the control, AP or GERD subjects. The well correlated expression in P2X3 gene with TRPV1 (r = 0.46, P = 0.002), NGF (r = 0.54, P = 0.0002), and GDNF (r = 0.64, P = 0.0001) was found. The P2X7 gene expressions also well correlated with TRPV1 (r = 0.47, P = 0.002), NGF (r = 0.32, P = 0.037), and GDNF (r = 0.42, P = 0.005). These results suggest that chronic esophagitis increases mRNA expressions of P2X3 and P2X7 receptors accompanied by up-regulation of TRPV1 and neurotrophic factors (NGF and GDNF). These genetical alterations in esophageal mucosa might mediate sensitization of inflamed human esophagus.
...
PMID:Evidence for up-regulation of purinergic receptor genes associating with TRPV1 receptors and neurotrophic factors in the inflamed human esophagus. 2533 28

Patients with coronary artery disease (CAD) are destined to lifelong antiplatelet therapy in form of aspirin (acetylsalicylic acid) alone, or in combination with other P2Y2 inhibitors. Proton pump inhibitors (PPIs) are the preferred agents for the treatment and prophylaxis of gastrointestinal injury associated with nonsteroidal anti-inflammatory drug or acetylsalicylic acid or both,1 but recent data has raised questions about their association with negative cardiovascular events. We report 2 cases of patients with known CAD presented with chest pain mimicking angina pectoris that successfully resolved on discontinuation of the PPIs. One male and one female patient with known history of CAD receiving PPIs were referred to us with symptoms of refractory angina that was unresponsive to conventional optimized medical therapy. The angina was reported to be related to exertion in both the patients. Neither patient had a diagnosis of Prinzmetal angina or peptic ulcer disease; however, both patients reported a history of gastroesophageal reflux disease. Both patients were on dual antiplatelet therapy. No ischemic changes on the electrocardiogram were noted for either patient. Patient 1 had an exercise stress test that was negative for any inducible ischemia whereas patient 2 had no obstructive lesion seen on coronary angiography. Both patients reported to be symptom free after discontinuation of PPIs at 8 months of follow-up. It is our opinion that a relationship between PPIs and angina-like chest pain is plausible, as these 2 cases demonstrate the causative role of PPIs in precipitation of their symptoms. We postulate that this association should be considered in differential diagnosis of chest pain. In light of above findings we suggest that this is hypothesis generating and we are exploring the role of PPIs in patients with history of CAD and refractory angina-like symptoms despite complete revascularization.
 ...
PMID:The Unknown Association of PPIs With Chest Pain in Patients With Known, Treated Coronary Artery Disease-A Diagnostic Dilemma. 2790 88