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- Title
Cloning and pharmacological characterization of the equine adenosine A<sub>3</sub> receptor.
- Authors
BRANDON, C. I.; VANDENPLAS, M.; DOOKWAH, H.; MURRAY, T. F.
- Abstract
The aim of this study was to establish a heterologous expression system for the equine adenosine A3 receptor (eA3-R) in an effort to ascertain its pharmacologic profile. Initially, radioligand binding assays identified clones expressing the eA3-R in human embryonic kidney cells (HEK) based on the specific binding of [125I]AB-MECA. Subsequently, adenylate cyclase assays were utilized to demonstrate functional coupling of the eA3-R to the G-protein/adenylate cyclase system. Equilibrium competition binding assays were then performed using selective and non-selective A3 agonists and antagonists. Results from these experiments revealed a rank order of agonist potency to be IB-MECA > NECA > CGS21680, and an antagonist potency of MRS1220 > ZM241385 > 8- p-sulphophenyltheophylline; these rank orders were in agreement with that of other mammalian A3-R's. Lastly, NF- κB reporter gene assays revealed an IB-MECA concentration-dependent inhibition of TNF α-stimulated NF- κB activity. These results indicate that the heterologously expressed eA3-R is functional, has a pharmacological profile similar to that of other mammalian A3 receptors, and its activation has an inhibitory effect on a key regulatory pathway in the inflammatory response. Thus, the eA3-R may serve as a pharmacological target in the treatment of equine inflammatory disease.
- Subjects
ADENOSINES; RADIOLIGAND assay; HORSE diseases; INFLAMMATION; PHARMACOLOGY; DRUG development
- Publication
Journal of Veterinary Pharmacology & Therapeutics, 2006, Vol 29, Issue 4, p255
- ISSN
0140-7783
- Publication type
Article
- DOI
10.1111/j.1365-2885.2006.00748.x