Pharmacokinetics of Eltenac in the horse after intravenous administration

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 TNFα-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.