Cloning and pharmacological characterization of the equine adenosine A 3 receptor

C. I. Brandon, M. Vandenplas, H. Dookwah, Thomas F. Murray

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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 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.

Original languageEnglish
Pages (from-to)255-263
Number of pages9
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume29
Issue number4
DOIs
Publication statusPublished - Aug 2006
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • veterinary(all)

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