Mode of action of thrombin in the rabbit aorta
Mode of action of thrombin in the rabbit aorta
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凝血酶在兔主动脉中的作用方式
DOI：
10.1111/j.1476-5381.1995.tb15895.x
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发表时间：
1995
影响因子：
7.3
通讯作者：
G. Drapeau
中科院分区：
文献类型：
--
作者：
D. Godin;F. Rioux;F. Marceau;G. Drapeau
1凝血酶是一种血管活性蛋白酶，它通过裂解G蛋白偶联受体的N端胞外结构域激活G蛋白偶联受体，从而引起兔主动脉收缩。在凝血酶裂解后，与新暴露的N端相对应的合成肽已被证明可以在兔主动脉中复制凝血酶的一些活性。通过使用一系列抑制剂，研究了兔主动脉对凝血酶和合成肽的收缩反应中涉及的细胞内通路。采用类似的方法来表征凝血酶对来自同一组织的培养平滑肌细胞（SMCs）的有丝分裂作用。本研究结果表明，兔主动脉对凝血酶的收缩反应依赖于蛋白激酶C （PKC）的激活，不依赖于细胞外钙。对凝血酶的收缩反应可以通过与N端受体序列相关的肽激动剂完全复制。然而，凝血酶和合成肽的收缩作用机制似乎存在微妙的差异，因为PKC激活和细胞外钙被发现参与了合成肽的收缩作用。在培养的SMCs中，凝血酶和合成肽都增加了肌醇磷酸的周转；然而，只有凝血酶引起有丝分裂效应，这种效应发生在凝血酶浓度远低于显著增加肌醇磷酸盐周转率所需的浓度时。酪氨酸激酶途径的激活参与了凝血酶对主动脉SMCs的有丝分裂作用。综上所述，这些结果表明，在兔主动脉中，凝血酶和与N端凝血酶受体序列相关的合成肽的作用方式存在细微差异。
1 Thrombin is a vasoactive protease that elicits the contraction of the rabbit aorta by activating a G‐protein coupled receptor through cleavage of its N‐terminal extracellular domain. Synthetic peptides corresponding to the newly exposed N‐terminus, following thrombin cleavage, have been shown to reproduce some of the activities of thrombin in the rabbit aorta. 2 Intracellular pathways involved in the contractile response of the rabbit aorta to thrombin and synthetic peptides were examined by use of a series of inhibitors. A similar method was applied to characterize the mitogenic effect of thrombin on cultured smooth muscle cells (SMCs) derived from the same tissue. 3 Results from this study indicate that the contractile response of the rabbit aorta to thrombin is dependent on the activation of protein kinase C (PKC) and independent of extracellular calcium. The contractile response to thrombin can be fully reproduced by peptide agonists related to the N‐terminal receptor sequence. However, subtle differences seem to exist between the mechanism of the contractile effect of thrombin and of the synthetic peptides, as both PKC activation and extracellular calcium were found to participate in the contractile effect of the synthetic peptides. 4 In cultured SMCs, both thrombin and the synthetic peptides increased inositol phosphate turnover; however, only thrombin elicited a mitogenic effect, which occurs at thrombin concentrations well below those needed to increase inositol phosphate turnover significantly. Activation of a tyrosine kinase pathway is involved in the mitogenic effect of thrombin on aortic SMCs. 5 Altogether these results suggest the existence of subtle differences between the mode of action of thrombin and of synthetic peptides related to the N‐terminal thrombin receptor sequence, in the rabbit aorta.
钙拮抗剂诱导血管舒张的机制。
DOI：
10.1146/annurev.pa.23.040183.002105
发表时间：
1983
影响因子：
12.5
作者：
Cauvin,C;Loutzenhiser,R;VanBreemen,C
通讯作者：
VanBreemen,C