multiple p2y receptors mediate contraction in guinea pig mesenteric vein vasoconstrictor responses to exogenous adenine and pyrimidine nucleotides were measured in endotheliumdenuded segments of guinea pig mesenteric vein and compared with responses in mesenteric artery the rank order of potency for nucleotides in veins was 2mesadp 2mesatp utp atpgammas alphabetameatp udp atp adp betagammadmeatp betagammalmeatp in contrast 2mesadp utp and udp were inactive in arteries and the rank order of potency of other nucleotides differed that is alphabetameatp beta gammadmeatp betagammalmeatp atpgammas 2mesatp atp adp in veins utp atp and 2mesatp were more efficacious contractile agents than alphabeta meatp in addition the ability to desensitize responses to these nucleotides and inhibit them with various blockers differed the response to alphabetameatp in veins exhibited rapid desensitization and was inhibited by pyridoxalphosphate6azophenyl24disulfonic acid tetrasodium ppads and suramin the response to 2mesatp in veins did not desensitize nor was it inhibited by prior alphabetameatp desensitization but it was inhibited by ppads suramin and the selective p2y1 receptor antagonist adenosine 35bisphosphate abp 10100 microm responses to atp and utp in veins did not desensitize and were not inhibited by ppads suramin abp or alpha betameatp 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 utppreferring 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