Regional variation in P2 receptor expression in the rat pulmonary arterial circulation

The P2 receptors that mediate contraction of the rat isolated small (SPA, 200–500 μm i.d.) and large (LPA, 1–1.5 m M i.d.) intrapulmonary arteries were characterized. In endothelium‐denuded vessels the contractile order of potency was α,β‐methyleneATP (α,β‐meATP)>>UDP=UTP=ATP=2‐methylthioATP>ADP in the SPA and α,β‐meATP=UTPUDP>2‐methylthioATP, ATP>>ADP in the LPA. α,β‐meATP, 2‐methylthioATP and ATP had significantly greater effects in the SPA than the LPA ( P <0.001), but there was no difference in the potency of UTP or UDP between the vessels. In the SPA, P2X 1 receptor desensitisation by α,β‐meATP (100 μ M ) inhibited contractions to α,β‐meATP (10 n M –300 μ M ), but not those to UTP or UDP (100 n M –300 μ M ). In the LPA, prolonged exposure to α,β‐meATP (100 μ M ) did not desensitize P2X receptors. Pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS), suramin and reactive blue 2 (RB2) (30–300 μ M ) inhibited contractions evoked by α,β‐meATP. UTP and UDP were potentiated by PPADS, unaffected by RB2 and inhibited, but not abolished by suramin. 1 and 3 m M suramin produced no further inhibition, indicating suramin‐resistant components in the responses to UTP and UDP. Thus, both P2X and P2Y receptors mediate contraction of rat large and small intrapulmonary arteries. P2Y agonist potency and sensitivity to antagonists were similar in small and large vessels, but P2X agonists were more potent in small arteries. This indicates differential expression of P2X, but not P2Y receptors along the pulmonary arterial tree.British Journal of Pharmacology (2002) 137 , 637–646. doi: 10.1038/sj.bjp.0704915