CHARACTERIZATION OF P2X-RECEPTORS IN RABBIT ISOLATED EAR ARTERY

1. The isolated central ear artery of the rabbit contracts in response to adenosine 5'-triphosphate (ATP) and analogues, effects proposed to be mediated by stimulation of P(2x)-receptors. We have extended the characterization of the purinoceptor in this tissue by examining the effects of a series of receptor agonists. The study was designed in such a way as to avoid factors which normally limit attempts to classify receptors on the basis of agonist potency orders. 2. D-α,β-methylene ATP (D-α,β-meATP), D-β,γ-methylene ATP (D-β,γ-meATP), L-β,γ-methylene ATP (L-β,γ-meATP), 2-methylthio-D-ATP (2-MeSATP) and ATP produced concentration-related contractions of the ear artery with similar maximum responses, suggesting that they were full agonists. Selective desensitization of P(2x)-receptors abolished or greatly reduced responses to D-α,β-meATP, L-β,γ-meATP, D-β,γ-meATP and 2-MeSATP. Responses to ATP were inhibited by desensitization but a significant resistant component was still apparent. 3. D-α,β-meATP was the most potent agonist tested (pA50 6.47 ± 0.04) being 2138 times more potent than ATP and approximately 9 times more potent than L-β,γ-meATP. The agonist potency order was: D-α,β-meATP > L-β,γ-meATP > D-β,γ-meATP ≥ 2-MeSATP > ATP. This is generally consistent with the order proposed for P(2x)-receptors. The relative potencies of P(2x)-agonists in the rabbit ear artery show both similarities to and differences from data obtained in other smooth muscle preparations.