Cyclic AMP-independent CGRP8-37-sensitive receptors mediate adrenomedullin-induced decrease of CaCl2-contraction in pregnant rat mesenteric artery.
Cyclic AMP-independent CGRP8-37-sensitive receptors mediate adrenomedullin-induced decrease of CaCl2-contraction in pregnant rat mesenteric artery.
复制标题
环状 AMP 独立的 CGRP8-37 敏感受体介导肾上腺髓质素诱导的怀孕大鼠肠系膜动脉 CaCl2 收缩的减少。
DOI：
10.1159/000109075
复制
发表时间：
2008
影响因子：
1.7
通讯作者：
Yallampalli,Chandra
中科院分区：
文献类型：
--
作者：
Ross,GraciousR;Yallampalli,Uma;Yallampalli,Chandra
目的验证肾上腺髓质素可减少妊娠大鼠去极化内皮剥脱肠系膜动脉内不依赖钾通道的钙内流的假说。结果肾上腺髓质素能减轻cacl2引起的收缩，受体拮抗剂降钙素基因相关肽（CGRP） 8-37能逆转这种作用，而肾上腺髓质素22-52不能。SQ22536抑制腺苷酸环化酶不能阻止肾上腺髓质素对cacl2诱导的收缩的作用。肾上腺髓质素不抑制去极化诱导的钙进入离体血管平滑肌。calyculin A对肌球蛋白轻链（MLC）磷酸酶的抑制作用逆转了肾上腺髓质素对亚毫摩尔浓度cacl2引起的收缩的作用，而肾上腺髓质素仍然抑制较高浓度cacl2引起的收缩。然而，MLC磷酸酶的调控亚基——磷酸化肌球蛋白磷酸酶靶1与总肌球蛋白磷酸酶靶1的比例并没有随着肾上腺髓质素的变化而改变，这表明MLC磷酸酶缺乏激活。有趣的是，非特异性蛋白磷酸酶抑制剂氟化钠完全阻断了肾上腺髓质素对cacl2诱导的收缩的作用。肾上腺髓质素抑制细胞内储存钙的动员。结论肾上腺髓质素通过CGRP 8 - 37敏感受体抑制cacl2诱导的收缩，但不影响钙内流，可能通过激活蛋白磷酸酶而非环腺苷单磷酸途径。抑制细胞内钙释放是肾上腺髓质素在血管平滑肌钙稳态中发挥的另一个作用。
ObjectivesWe tested the hypothesis that adrenomedullin reduces calcium influx independent of potassium channels in depolarized endothelium-denuded mesenteric artery from pregnant rats.ResultsAdrenomedullin reduced the CaCl 2-induced contraction, while the receptor antagonist calcitonin gene-related peptide (CGRP) 8–37, but not adrenomedullin 22–52, reversed these effects. Adenylate cyclase inhibition by SQ22536 did not prevent adrenomedullin effects on CaCl 2-induced contraction. Adrenomedullin did not inhibit depolarization-induced calcium entry to isolated vascular smooth muscle. Inhibition of myosin light-chain (MLC) phosphatase by calyculin A reversed the effects of adrenomedullin on contraction caused by submillimolar concentrations of CaCl 2, while adrenomedullin still inhibited contraction caused by higher concentrations of CaCl 2. However, the ratio of phosphorylated to total myosin phosphatase target 1, the regulatory subunit of MLC phosphatase, did not change with adrenomedullin, indicating a lack of MLC phosphatase activation. Interestingly, sodium fluoride, a nonspecific protein phosphatase inhibitor, completely blocked the effect of adrenomedullin on CaCl 2-induced contraction. Adrenomedullin inhibited calcium mobilization from intracellular stores induced by thapsigargin.ConclusionAdrenomedullin inhibits CaCl 2-induced contraction, without affecting calcium influx, through a CGRP 8–37-sensitive receptor, but not using the cyclic adenosine monophosphate pathway, probably through activation of protein phosphatases. Inhibition of intracellular calcium release is an additional role played by adrenomedullin in calcium homeostasis in vascular smooth muscle.