Human mast cell tryptase attenuates the vasodilator activity of calcitonin gene-related peptide.

Human mast cell tryptase attenuates the vasodilator activity of calcitonin gene-related peptide.
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人肥大细胞类胰蛋白酶减弱降钙素基因相关肽的血管舒张活性。

DOI:
10.1016/0006-2952(92)90498-8
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发表时间:
1992
影响因子:
5.8
通讯作者:
Timothy Williams
Timothy Williams
中科院分区:
医学2区
文献类型:
--
作者:
A. F. Walls;S. D. Brain;Anita Desai;P. J. Jose;Elaine Hawkings;M. K. Church;Timothy Williams

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降钙素基因相关肽(CGRP)定位于感觉神经并从感觉神经释放。它是一种有效的长效血管扩张剂,被认为在控制血流中发挥作用。使用HPLC和三氯乙酸沉淀技术,我们已经研究了人肥大细胞裂解物和肥大细胞类胰蛋白酶的纯化制剂降解CGRP的能力。我们发现CGRP被类胰蛋白酶有效地切割(Km = 6.8 10− 6 mol/L,37°)。抗痛剂、亮抑酶肽、N-α-对甲苯磺酰-L-赖氨酸氯甲基酮、苯甲脒和抑肽酶对酶活性有抑制作用,而大豆胰蛋白酶抑制剂和N-对甲苯磺酰-L-苯丙氨酸氯甲基酮对酶活性无抑制作用。纯化的皮肤肥大细胞裂解物的CGRP的降解表现出类似的抑制模式,表明类胰蛋白酶可能是主要的酶参与。类胰蛋白酶的活性不受肝素存在的影响。孵育的CGRP类胰蛋白酶导致其血管扩张活性的损失所观察到的仓鼠颊囊微血管的活体显微镜。CGRP预孵育类胰蛋白酶未能放松小动脉时,局部添加。这表明,类胰蛋白酶的CGRP的催化可能是一个重要的手段,通过这种神经肽的活性在体内调节。
Calcitonin gene-related peptide (CGRP) is localized in and released from sensory nerves. It is a potent and long acting vasodilator which has been suggested to play a role in the control of blood flow. Using HPLC and trichloroacetic acid precipitation techniques, we have examined the ability of human mast cell lysates and a purified preparation of mast cell tryptase to degrade CGRP. We found that CGRP is effectively cleaved by tryptase (K m= 6.8 10− 6 mol/L at 37°). Enzymatic activity was inhibited by antipain, leupeptin, N-α-p-tosyl-l-lysine chloromethyl ketone, benzamidine or aprotinin, but not by soybean trypsin inhibitor or N-tosyl-l-phenylalanine chloromethyl ketone. The degradation of CGRP by lysates of purified skin mast cells showed a similar pattern of inhibition suggesting that tryptase may be the major enzyme involved. The activity of tryptase was not affected by the presence of heparin. Incubation of CGRP with tryptase resulted in a loss of its vasodilator activity as observed by intravital microscopy of the hamster cheek pouch microvasculature. CGRP preincubated with tryptase failed to relax arterioles when added topically. It is suggested that the catalysis of CGRP by tryptase could represent an important means by which the activity of this neuropeptide is regulated in vivo.
人类肥大细胞中胰凝乳蛋白酶样蛋白酶的鉴定。
DOI: --
发表时间: 1986
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Schechter,NM;Choi,JK;Slavin,DA;Deresienski,DT;Sayama,S;Dong,G;Lavker,RM;Proud,D;Lazarus,GS
通讯作者: Lazarus,GS
DOI: 10.1172/jci114051
发表时间: 1989-05-01
影响因子: 15.9
作者:
SCHWARTZ, LB;YUNGINGER, JW;DULL, D
通讯作者: DULL, D
肥大细胞类胰蛋白酶和糜酶逆转雪貂中血管活性肠肽诱导的气道平滑肌松弛。
DOI: --
发表时间: 1989
期刊: The Journal of pharmacology and experimental therapeutics
影响因子: --
作者:
Franconi,GM;Graf,PD;Lazarus,SC;Nadel,JA;Caughey,GH
通讯作者: Caughey,GH
DOI: 10.1172/jci114344
发表时间: 1989-11-01
影响因子: 15.9
作者:
GRUBER, BL;MARCHESE, MJ;RAMAMURTHY, NS
通讯作者: RAMAMURTHY, NS
来自人肺肥大细胞的纯化类胰蛋白酶的纤维蛋白原分解活性。
DOI: --
发表时间: 1985
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Schwartz,LB;Bradford,TR;Littman,BH;Wintroub,BU
通讯作者: Wintroub,BU