Glucose-induced downregulation of angiotensin II and arginine vasopressin receptors in cultured rat aortic vascular smooth muscle cells. Role of protein kinase C.
Glucose-induced downregulation of angiotensin II and arginine vasopressin receptors in cultured rat aortic vascular smooth muscle cells. Role of protein kinase C.
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培养的大鼠主动脉血管平滑肌细胞中葡萄糖诱导的血管紧张素 II 和精氨酸加压素受体下调。
DOI：
10.1172/jci116079
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Schrier,RW
中科院分区：
文献类型：
--
作者：
Williams,B;Tsai,P;Schrier,RW
早期糖尿病的特征是对升压激素的反应受损和升压受体下调。本研究探讨了细胞外葡萄糖浓度升高对血管紧张素II（AII）和精氨酸加压素（AVP）受体动力学在培养的大鼠血管平滑肌细胞（VSMC）的影响。Scatchard分析[3 H]AVP和125 I-AII与融合VSMC的结合表明，高葡萄糖浓度（20 mM）同样抑制AVP和AII表面受体Bmax，但不影响受体Kd。这种受体下调没有再现的渗透控制培养基含有L-葡萄糖或甘露醇。受体下调在15-20 mM的葡萄糖浓度下最大，并且需要24-48 h才能达到最大效果。细胞外葡萄糖浓度的正常化允许AVP和AII结合在48小时内完全恢复。受体下调与AVP和AII刺激的细胞内信号传导和细胞收缩有关。高糖诱导VSMC蛋白激酶C（PKC）的持续激活，这是防止与H-7共孵育。H-7还显著减弱葡萄糖诱导的VSMC上AVP和AII受体的下调。这项研究证明了一种新的细胞机制，即高细胞外葡萄糖浓度直接和独立地下调升压激素受体及其功能的血管组织通过葡萄糖刺激的PKC激活。
Early diabetes mellitus is characterized by impaired responses to pressor hormones and pressor receptor downregulation. The present study examined the effect of elevated extracellular glucose concentrations on angiotensin II (AII) and arginine vasopressin (AVP) receptor kinetics in cultured rat vascular smooth muscle cells (VSMC). Scatchard analysis of [3H]AVP and 125I-AII binding to confluent VSMC showed that high glucose concentrations (20 mM) similarly depressed AVP and AII surface receptor Bmax but did not influence receptor Kd. This receptor downregulation was not reproduced by osmotic control media containing either L-glucose or mannitol. Receptor downregulation was maximal at a glucose concentration of 15-20 mM and required 24-48 h for a maximum effect. Normalization of the extracellular glucose concentration allowed complete recovery of AVP and AII binding within 48 h. Receptor downregulation was associated with depressed AVP and AII-stimulated intracellular signaling and cell contraction. High glucose concentrations induced a sustained activation of protein kinase C (PKC) in VSMC, which was prevented by coincubation with H-7. H-7 also markedly attenuated glucose-induced downregulation of AVP and AII receptors on VSMC. This study demonstrates a novel cellular mechanism whereby high extracellular glucose concentrations directly and independently downregulate pressor hormone receptors and their function on vascular tissue via glucose-stimulated PKC activation.