Receptor mechanism of thrombin-mediated pulmonary vasodilation in neonates.
Receptor mechanism of thrombin-mediated pulmonary vasodilation in neonates.
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新生儿凝血酶介导的肺血管舒张的受体机制。
DOI：
10.1152/ajplung.1993.265.4.l355
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Malik,AB
中科院分区：
文献类型：
--
作者：
Pinheiro,JM;Andersen,TT;Malik,AB
最近发现的一个肽序列，在凝血酶受体的NH2末端被蛋白水解性切割后，模拟了α-凝血酶的一些细胞效应。为了确定血管活性是否需要凝血酶的蛋白分解作用，我们研究了凝血酶受体(TRPs)修饰的凝血酶和人工合成的凝血酶受体(TRPs)NH2末端肽序列对血管的影响。1-6日龄仔猪的肺以60ml/min的恒定流量灌流循环林格白蛋白溶液。我们用双阻断法测量了注射人α-凝血酶、改良凝血酶和Trp-14和Trp-7(即被切割的凝血酶受体的14和7个氨基酸NH2末端的多肽)后的肺动脉压(PPA)和肺血管阻力的节段分布。α-凝血酶引起PPA的快速和一过性下降；血管扩张反应的幅度和持续时间[一半恢复时间(t1/2R)]呈浓度依赖性[t1/2R值分别为1.4+/-0.1和3.3+/-2.4min(均值+/-SE)，10(-10)M和10(-9)M时分别为3.3+/-2.4分钟]。血管扩张主要是由于毛细血管前阻力的减少。蛋白水解性的，但结合受损的伽马-凝血酶是一种不那么有效的血管扩张剂，而蛋白水解性不活跃的D-苯丙氨酰丙氨基-精氨酸-氯甲基酮(PPACK)-α-凝血酶不能诱导血管扩张。Trp-14也是一种肺血管扩张剂，在10(-7)M的浓度下，t1/2r值为0.8+/-0.09min；Trp-14和Trp-7的效力都比等摩尔α-凝血酶低约3个对数。
A recently identified peptide sequence exposed after proteolytic cleavage of the NH2-terminus of the thrombin receptor mimics some cellular effects of alpha-thrombin. To determine whether a proteolytic action of thrombin is required for vasoactivity, we examined the vascular effects of modified thrombins and synthetic NH2-terminus peptide sequences of the thrombin receptor (TRPs) in isolated piglet lungs. Lungs of piglets 1-6 days old were perfused with recirculating Ringer-albumin solution at a constant flow of 60 ml/min. We measured the pulmonary artery pressure (Ppa) and segmental distribution of pulmonary vascular resistance (using the double occlusion method) in response to injections of human alpha-thrombin, modified thrombins, and TRP-14 and TRP-7 (i.e., 14 and 7 amino acid NH2-terminus peptides of the cleaved thrombin receptor). alpha-Thrombin produced a rapid and transient decrease in Ppa; the magnitude and duration [time for one-half recovery (t1/2 R)] of the vasodilation responses were concentration dependent [t1/2 R values of 1.4 +/- 0.1 and 3.3 +/- 2.4 min (mean +/- SE) at concentrations of 10(-10) and 10(-9) M, respectively]. The vasodilation was due primarily to a decrease in precapillary resistance. Proteolytically active, but binding-impaired gamma-thrombin was a less potent vasodilator and proteolytically inactive D-phenylalanyl-prolyl-arginine-chloromethyl ketone (PPACK)-alpha-thrombin did not induce vasodilation. TRP-14 was also a pulmonary vasodilator with a t1/2R value of 0.8 +/- 0.09 min at a concentration of 10(-7) M; both TRP-14 and TRP-7 were approximately 3-log less potent than equimolar alpha-thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)