Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
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Target Concepts:
Gene/Protein
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Query: UMLS:C0314719 (
dry eye
)
2,625
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Tear hyperosmolarity is a key event in
dry eye
. In this work, we analyzed whether hyperosmolar challenge induces ATP release on the ocular surface. Moreover, as extracellular ATP can activate
P2X7 receptor
, the changes in
P2X7
protein levels and its involvement in pathological process triggered by hypertonic treatment were also examined. High-performance liquid chromatography analysis revealed that ATP levels significantly increased in human corneal and conjunctival epithelial cells exposed to hyperosmotic challenge as well as in
dry eye
patients as compared to control subjects. A significant reduction in cell viability was detected after hyperosmolar treatment, indicating that the rise in ATP release was mainly due to cell lysis/death. Additionally, vesicular nucleotide transporter was identified in both cell lines and their protein expression was upregulated in hypertonic media.
P2X7 receptor
truncated form together with the full-length form was identified in both cell lines, and experiments using specific antagonist and agonist for
P2X7
indicated that this receptor did not mediate cell death induced by hyperosmolar stress. In conclusion, hyperosmotic stress induces ATP release. Extracellular ATP can activate
P2X7 receptor
leading to cytotoxicity in many cells/tissues; however, this does not occur in human corneal and conjunctival epithelial cells. In these cells, the presence of
P2X7 receptor
truncated form together with the full-length form hinders a
P2X7
apoptotic behavior on the ocular surface.
...
PMID:Hyperosmotic stress induces ATP release and changes in P2X7 receptor levels in human corneal and conjunctival epithelial cells. 2817 24
Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990's when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A
2A
receptor antagonists are promising for the treatment of Parkinson's disease. Clopidogrel, a P2Y
12
antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y
12
receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y
2
receptor agonist, is being used for the treatment of
dry eye
. P2X3 receptor antagonists have been developed that are orally bioavailable and stable
in vivo
and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to
P2X7
receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.
...
PMID:Purinergic Signalling: Therapeutic Developments. 2899 32
