ATP and UDP constrict rat intrapulmonary arteries, but which receptors mediate these actions is unclear. Here we used selective agonists and antagonists, along with measurements of P2Y receptor expression, to characterise the receptor subtypes involved. Isometric tension was recorded from endothelium-denuded rat intrapulmonary artery rings (i.d. 200-500 μm) mounted on a wire myograph. Expression of P2Y receptor subtype expression was determined using RT-PCR with receptor-specific oligonucleotide primers. The selective P2Y1 agonist MRS2365 induced small, concentration-dependent contractions that were inhibited by the P2Y1 antagonist MRS2179. Contractions evoked by ATP were unaffected by MRS2179, but inhibited by about one third by the P2Y12 antagonist AR-C69931MX. Combined blockade of P2X1 and P2Y12 receptors virtually abolished the response to ATP. ADP also evoked contractions that were abolished by AR-C69931MX. The selective P2Y6 receptor agonist, PSB 0474, evoked concentration-dependent contractions and was approximately 3-times more potent than UDP, but the P2Y14 agonist, UDP-glucose, had no effect. Contractions evoked by UDP were inhibited by the P2Y6 receptor antagonist, MRS2578, but not the CysLT1 antagonist, MK571. Higher concentrations of MRS2578 inhibited contractions to KCl and so were not studied further. mRNA for P2Y1, P2Y6 and P2Y12 receptors was identified, but this could not be correlated with protein expression. Our working model is that P2Y12 and P2X1 receptors are present in rat intrapulmonary arteries and together mediate ATP-induced vasoconstriction. Contractile P2Y6, but not P2Y14 or CysLT1 receptors are also present and are a major site through which UDP evokes constriction.
- Received July 3, 2012.
- Revision received September 17, 2012.
- Accepted September 17, 2012.
- The American Society for Pharmacology and Experimental Therapeutics