Multiple P2Y receptors mediate contraction in guinea pig mesenteric vein

Vasoconstrictor responses to exogenous adenine and pyrimidine nucleotides were measured in endothelium-denuded segments of guinea pig mesenteric vein and compared with responses in mesenteric artery. The rank order of potency for nucleotides in veins was: 2-MeSADP = 2-MeSATP > UTP > ATPγS = α,βMeATP > UDP = ATP > ADP >> β,γ-D-MeATP = β,γ-L-MeATP. In contrast 2-MeSADP, UTP, and UDP were inactive in arteries, and the rank order of potency of other nucleotides differed; that is, α,βMeATP > β,γ-D-MeATP > β,γ-L-MeATP = ATPγS = 2-MeSATP > ATP > ADP. In veins, UTP, ATP, and 2-MeSATP were more efficacious contractile agents than α,β MeATP. In addition, the ability to desensitize responses to these nucleotides and inhibit them with various blockers differed. The response to α,βMeATP in veins exhibited rapid desensitization and was inhibited by pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid tetrasodium (PPADS) and suramin. The response to 2-MeSATP in veins did not desensitize; nor was it inhibited by prior α,βMeATP desensitization, but it was inhibited by PPADS, suramin, and the selective P2Y₁ receptor antagonist adenosine 3′,5′-bisphosphate (ABP, 10–100 μM). Responses to ATP and UTP in veins did not desensitize and were not inhibited by PPADS, suramin, ABP, or α,βMeATP desensitization. In conclusion, our results suggest that venous contraction to a variety of nucleotides is mediated in large part by P2Y receptors including P2Y₁ receptors and an UTP-preferring P2Y receptor. A small component of contraction also appears to be mediated by P2X₁ receptors. This receptor profile differs markedly from that of mesenteric arteries in which P2X₁ receptors predominate.