CHARACTERIZATION OF ENDOTHELIN-BINDING SITES IN HUMAN SKIN AND THEIR REGULATION IN PRIMARY RAYNAUDS-PHENOMENON AND SYSTEMIC-SCLEROSIS
CHARACTERIZATION OF ENDOTHELIN-BINDING SITES IN HUMAN SKIN AND THEIR REGULATION IN PRIMARY RAYNAUDS-PHENOMENON AND SYSTEMIC-SCLEROSIS
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DOI：
10.1111/1523-1747.ep12360103
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发表时间：
1993-07-01
影响因子：
6.5
通讯作者：
POLAK, JM
中科院分区：
文献类型：
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作者：
KNOCK, GA;TERENGHI, G;POLAK, JM
内皮素（ET）通过多种受体亚型介导血管收缩和血管舒张活性，参与人体皮肤血流量和血管张力的调控，并可能参与原发性雷诺现象和系统性硬化症的异常血管收缩反应。使用体外放射自显影，我们已经研究了内皮素结合特性和受体亚型的人皮肤，并试图提供证据内皮素受体调节原发性或继发性雷诺现象患者的皮肤。特异性I-125-ET-1和I-125-ET-3结合位点定位于表皮下神经丛和真皮乳头的微血管、大血管、汗腺、表皮和毛囊。ET（A）和ET（B）受体均存在于微血管和其他结构中。皮肤血管内皮素受体的异质性表明，在人类皮肤血管收缩和血管舒张通路的自分泌/旁分泌调节剂的ET的作用。在表皮和毛囊中存在结合位点提示内皮素在人皮肤中可能具有促有丝分裂功能。与对照组相比，系统性硬化症患者皮肤微血管内皮素结合密度显著较高（p < 0.05），但雷诺现象患者无显著差异。在雷诺现象和系统性硬化症中，ET受体缺乏下调可能有助于这些疾病中血管痉挛的发病机制。
Endothelin (ET), which mediates vasoconstrictor and vasodilator activities via multiple receptor subtypes, has been implicated in the control of blood flow and vascular tone in human skin, and possibly in the abnormal vasoconstrictor response in primary Raynaud's phenomenon and systemic sclerosis. Using in vitro autoradiography we have examined the endothelin-binding characteristics and receptor subtypes of human skin, and sought to provide evidence for endothelin receptor regulation in skin from patients with primary or secondary Raynaud's phenomenon. Specific I-125-ET-1 and I-125-ET-3 binding sites were localized to microvessels of the sub-epidermal plexus and dermal papillae, larger blood vessels, sweat glands, epidermis, and hair follicles. Both ET(A) and ET(B) receptors were demonstrated in microvessels and other structures. ET receptor heterogeneity in skin vasculature suggests a role for ET as an autocrine/paracrine regulator of vasoconstrictor and vasodilator pathways in human skin. The presence of binding sites in epidermis and hair follicles suggests a possible mitogenic function for endothelin in human skin. Endothelin-binding density was significantly higher (p < 0.05) in microvessels of skin from patients with systemic sclerosis but not significantly different in Raynaud's phenomenon patients, compared to controls. Lack of down regulation of ET receptors in Raynaud's phenomenon and systemic sclerosis may contribute to the pathogenesis of vasospasm in these diseases.