{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:01:21Z","timestamp":1784199681330,"version":"3.55.0"},"reference-count":45,"publisher":"American Veterinary Medical Association (AVMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2003,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n\t\t\t\t<jats:p>\n\t\t\t\t\t<jats:bold>Objective<\/jats:bold>\u2014To determine the presence of adenosine\nreceptor subtypes A<jats:sub>1<\/jats:sub> and A<jats:sub>2a<\/jats:sub> in equine forebrain tissues\nand to characterize the interactions of caffeine\nand its metabolites with adenosine receptors in the\nCNS of horses.<\/jats:p>\n\t\t\t\t<jats:p>\n\t\t\t\t\t<jats:bold>Sample Population<\/jats:bold>\u2014Brain tissue specimens\nobtained during necropsy from 5 adult male research<\/jats:p>\n\t\t\t\t<jats:p>\n\t\t\t\t\t<jats:bold>Procedures<\/jats:bold>\u2014Membrane-enriched homogenates from\ncerebral cortex and striatum were evaluated by radioligand\nbinding assays with the A<jats:sub>1<\/jats:sub>-selective ligand\n[<jats:sup>3<\/jats:sup>H]DPCPX and the A<jats:sub>2a<\/jats:sub>-selective ligand\n[<jats:sup>3<\/jats:sup>H]ZM241385. Functional responses to adenosine\nreceptor agonists and antagonists were determined\nby a nucleotide exchange assay using [<jats:sup>35<\/jats:sup>S]-guanosine\n5'-(\u03b3-thio) triphosphate ([<jats:sup>35<\/jats:sup>S]GTP\u03b3S).<\/jats:p>\n\t\t\t\t<jats:p>\n\t\t\t\t\t<jats:bold>Results<\/jats:bold>\u2014Saturable high affinity [<jats:sup>3<\/jats:sup>H]DPCPX binding\n(A<jats:sub>1<\/jats:sub>) sites were detected in cerebral cortex and striatum,\nwhereas high-affinity [<jats:sup>3<\/jats:sup>H]ZM241385 binding\n(A<jats:sub>2a<\/jats:sub>) sites were detected only in striatum. Caffeine\nand related methylxanthines had similar binding affinities\nat A1 and A2a sites with rank orders of drug binding\naffinities (theophylline &gt; paraxanthine \u2265 caffeine\n&gt;&gt; theobromine) similar to other species. [<jats:sup>35<\/jats:sup>S]GTP\u03b3S\nexchange revealed that caffeine and its metabolites\nact as pure adenosine receptor antagonists at concentrations\nthat correspond to A<jats:sub>1<\/jats:sub> and A<jats:sub>2a<\/jats:sub> receptor\nbinding affinities.<\/jats:p>\n\t\t\t\t<jats:p>\n\t\t\t\t\t<jats:bold>Conclusions and Clinical Relevance<\/jats:bold>\u2014Results of our\nstudy affirm the presence of guanine nucleotide binding\nprotein linked adenosine receptors (ie, high-affinity\nA<jats:sub>1<\/jats:sub> and A<jats:sub>2a<\/jats:sub> adenosine receptors) in equine forebrain\ntissues and reveal the antagonistic actions by caffeine\nand several biologically active caffeine metabolites.\nAntagonism of adenosine actions in the equine CNS\nby these stimulants may be responsible for some\ncentral actions of methylxanthine drugs, including\nmotor stimulation and enhanced racing performance.\n(<jats:italic>Am J Vet Res<\/jats:italic> 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