Bronchoconstrictor effect of thrombin and thrombin receptor activating peptide in guinea‐pigs in vivo
Bronchoconstrictor effect of thrombin and thrombin receptor activating peptide in guinea‐pigs in vivo
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凝血酶和凝血酶受体激活肽对豚鼠体内支气管收缩作用
DOI：
10.1038/sj.bjp.0702303
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发表时间：
1999
影响因子：
7.3
通讯作者：
G. Cirino
中科院分区：
文献类型：
--
作者：
C. Cicala;M. Bucci;G. de Dominicis;Pat Harriot;L. Sorrentino;G. Cirino
凝血酶的几种细胞效应依赖于位于细胞表面的蛋白酶激活受体-1(PAR-1)的刺激。在被凝血酶激活后，PAR-1受体上的一个新的N末端多肽被揭开，它作为受体本身的捆绑配体发挥作用。合成肽称为凝血酶受体激活肽(Traps)，对应于未被掩蔽的N末端残基，具有多种凝血酶细胞效应，但缺乏催化活性。我们评价了静脉注射人α-凝血酶或凝血酶受体激活肽(TRAP-9)对麻醉、人工呼吸的豚鼠的支气管反应。静脉注射凝血酶(10 0 u kg−1)引起支气管收缩，再注射TRAP 9(1 mg kg−1)。动物静脉注射凝血酶抑制剂水飞蓟™(10 mg kg−1 )抑制凝血酶引起的支气管收缩，但不影响TRAP-9引起的支气管收缩。两种药物静脉注射均不引起大鼠的支气管收缩。凝血酶和TRAP-9的支气管收缩作用是耐受的；然而，在对凝血酶作用不敏感的动物中，TRAP-9仍然能够诱导支气管收缩，但反之亦然。耗尽循环中的血小板的动物可以预防凝血酶和TRAP-9引起的支气管收缩。支气管收缩与动脉血压的双相变化平行，其特征是低血压阶段之后是高血压阶段。凝血酶诱导的低血压不耐受，可被水牛™抑制；相反，高血压受耐受，不能被水牛™抑制。TRAP-9诱导的低血压和高血压既不耐受，也不能被水牛™抑制。我们的结果表明，凝血酶引起豚鼠支气管收缩的机制是需要其受体的蛋白水解性激活和暴露拴系配基多肽。凝血酶效应可能触发了血小板的激活。
Several thrombin cellular effects are dependent upon stimulation of proteinase activated receptor‐1 (PAR‐1) localized over the cellular surface. Following activation by thrombin, a new N‐terminus peptide is unmasked on PAR‐1 receptor, which functions as a tethered ligand for the receptor itself. Synthetic peptides called thrombin receptor activating peptides (TRAPs), corresponding to the N‐terminus residue unmasked, reproduce several thrombin cellular effects, but are devoid of catalytic activity. We have evaluated the bronchial response to intravenous administration of human α‐thrombin or a thrombin receptor activating peptide (TRAP‐9) in anaesthetized, artificially ventilated guinea‐pigs. Intravenous injection of thrombin (100 u kg−1) caused bronchoconstriction that was recapitulated by injection of TRAP‐9 (1 mg kg−1). Animal pretreatment with the thrombin inhibitor Hirulog™ (10 mg kg−1 i.v.) prevented thrombin‐induced bronchoconstriction, but did not affect bronchoconstriction induced by TRAP‐9. Both agents did not induce bronchoconstriction when injected intravenously to rats. The bronchoconstrictor effect of thrombin and TRAP‐9 was subjected to tolerance; however, in animals desensitized to thrombin effect, TRAP‐9 was still capable of inducing bronchoconstriction, but not vice versa. Depleting animals of circulating platelets prevented bronchoconstriction induced by both thrombin and TRAP‐9. Bronchoconstriction was paralleled by a biphasic change in arterial blood pressure, characterized by a hypotensive phase followed by a hypertensive phase. Thrombin‐induced hypotension was not subject to tolerance and was inhibited by Hirulog™; conversely, hypertension was subject to tolerance and was not inhibited by Hirulog™. Hypotension and hypertension induced by TRAP‐9 were neither subject to tolerance nor inhibited by Hirulog™. Our results indicate that thrombin causes bronchoconstriction in guinea‐pigs through a mechanism that requires proteolytic activation of its receptor and the exposure of the tethered ligand peptide. Platelet activation might be triggered by the thrombin effect.
油酸和博来霉素诱导的肺损伤大鼠肺灌洗中纤维蛋白转换途径的异常支持肺泡纤维蛋白沉积。
DOI：
--
发表时间：
1989
期刊：
The American journal of pathology
影响因子：
--
作者：
Idell,S;James,KK;Gillies,C;Fair,DS;Thrall,RS
通讯作者：
Thrall,RS
α-凝血酶增加胞质钙并诱导人气道平滑肌细胞增殖。
DOI：
10.1165/ajrcmb.13.2.7626288
发表时间：
1995
期刊：
American journal of respiratory cell and molecular biology.
影响因子：
--
作者：
PanettieriJr,RA;Hall,IP;Maki,CS;Murray,RK
通讯作者：
Murray,RK