Mutafova-Yambolieva V N, Carolan B M, Harden T K, Keef K D
Department of Physiology and Cell Biology, Anderson Medical Building, MS 352, University of Nevada School of Medicine, Reno, NV 89557-0046, USA.
Gen Pharmacol. 2000 Feb;34(2):127-36. doi: 10.1016/s0306-3623(00)00054-9.
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 > ATPgammaS = alpha,betaMeATP > UDP = ATP > ADP >> beta,gamma-D-MeATP = beta,gamma-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, alpha,betaMeATP > beta, gamma-D-MeATP > beta,gamma-L-MeATP = ATPgammaS = 2-MeSATP > ATP > ADP. In veins, UTP, ATP, and 2-MeSATP were more efficacious contractile agents than alpha,beta MeATP. In addition, the ability to desensitize responses to these nucleotides and inhibit them with various blockers differed. The response to alpha,betaMeATP 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 alpha,betaMeATP desensitization, but it was inhibited by PPADS, suramin, and the selective P2Y(1) receptor antagonist adenosine 3',5'-bisphosphate (ABP, 10-100 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 P2Y(1) receptors and an UTP-preferring P2Y receptor. A small component of contraction also appears to be mediated by P2X(1) receptors. This receptor profile differs markedly from that of mesenteric arteries in which P2X(1) receptors predominate.
在豚鼠肠系膜静脉内皮剥脱段测量了对外源性腺嘌呤和嘧啶核苷酸的血管收缩反应，并与肠系膜动脉中的反应进行了比较。静脉中核苷酸的效力排序为：2-甲硫腺苷二磷酸（2-MeSADP） = 2-甲硫三磷酸腺苷（2-MeSATP） > 尿苷三磷酸（UTP） > 三磷酸腺苷γ-硫代三磷酸（ATPγS） = α,β-甲基三磷酸腺苷（α,βMeATP） > 尿苷二磷酸（UDP） = 三磷酸腺苷（ATP） > 二磷酸腺苷（ADP） >> β,γ-D-甲基三磷酸腺苷（β,γ-D-MeATP） = β,γ-L-甲基三磷酸腺苷（β,γ-L-MeATP）。相比之下，2-MeSADP、UTP和UDP在动脉中无活性，其他核苷酸的效力排序不同；即α,βMeATP > β,γ-D-MeATP > β,γ-L-MeATP = ATPγS = 2-MeSATP > ATP > ADP。在静脉中，UTP、ATP和2-MeSATP比α,βMeATP是更有效的收缩剂。此外，使对这些核苷酸的反应脱敏并用各种阻滞剂抑制它们的能力也不同。静脉中对α,βMeATP的反应表现出快速脱敏，并被磷酸吡哆醛-6-偶氮苯基-2',4'-二磺酸四钠（PPADS）和苏拉明抑制。静脉中对2-MeSATP的反应不会脱敏；也不会被预先的α,βMeATP脱敏所抑制，但它被PPADS、苏拉明和选择性P2Y(1)受体拮抗剂3',5'-二磷酸腺苷（ABP，10 - 100微摩尔）抑制。静脉中对ATP和UTP的反应不会脱敏，也不会被PPADS、苏拉明、ABP或α,βMeATP脱敏所抑制。总之，我们的结果表明，静脉对多种核苷酸的收缩在很大程度上由P2Y受体介导，包括P2Y(1)受体和一种偏好UTP的P2Y受体。收缩的一小部分似乎也由P2X(1)受体介导。这种受体分布与肠系膜动脉明显不同，在肠系膜动脉中P2X(1)受体占主导。
