Characterization of P 2x ‐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 (pA 50 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.