Do adenosine A3 receptors exist

Abstract 1. 1. It has been suggested that adenosine A 1 receptors may be sub-divided into A 1 and A 3 types, based on the relative potencies of 5′- N -ethylcarboxamidoadenosine (NECA) and selected N 6 -substituted adenosine analogues. At A 1 receptors (rat adipocytes) N 6 -phenylisopropyladenosine (PIA) was reported to be approx. 100-fold more potent than NECA, whereas the compounds were equipotent at A 3 receptors (those in cardiac and neuronal preparations). 2. 2. The study reported here has systematically evaluated this proposal, the rank orders of potency of NECA, R - and S -PIA, N 6 -cyclopentyladenosine (CPA) and N 6 -cyclohexyladenosine (CHA) being determined in rat adipocytes, guinea-pig ileum and rat and guinea-pig atria. 3. 3. R -PIA, CHA and CPA were found to have consistent potencies relative to NECA across all 6 tissues, including rat adipocytes. The rank order was CPA ≥ CHA, R -PIA ≥ NECA > S -PIA. 4. 4. We conclude that the relative potencies of these agonists do not support the concept that adenosine A 1 receptors in rat adipocytes differ from those in neuronal and cardiac tissues.