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糜蛋白酶对兔眼压的影响。

Effect of chymase on intraocular pressure in rabbits.

作者信息

Konno Takashi, Maruichi Midori, Takai Shinji, Oku Hidehiro, Sugiyama Tetsuya, Uchibori Takehiro, Nagai Akihiko, Kogi Kentaro, Ikeda Tsunehiko, Miyazaki Mizuo

机构信息

Drug Research Section II, Fukushima Research Laboratories, Yuno, Iizaka-machi, Fukushima City, Fukushima, Japan.

出版信息

Eur J Pharmacol. 2005 Nov 7;524(1-3):132-7. doi: 10.1016/j.ejphar.2005.09.048. Epub 2005 Oct 25.

Abstract

Chymase is a chymotrypsin-like serine protease that is stored exclusively in the secretory granules of mast cells and converts big endothelins to endothelin-1 (1-31). The aim of this study was to evaluate the effect of chymase on intraocular pressure in rabbits. Chymase injection (3 and 10 mU) resulted in a trend toward increased intraocular pressure and a significant increase in intraocular pressure at a dose of 10 mU compared with the control. A specific chymase inhibitor, Suc-Val-Pro-Phe(P)(OPh)(2), attenuated the ocular hypertension induced by chymase. Endothelin-1 (1-31) also caused ocular hypertension, which was inhibited by a selective endothelin ET(A) receptor antagonist, cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123). Moreover, chymase-induced ocular hypertension was inhibited by BQ-123. These results suggest that chymase influences the regulation of intraocular pressure, and it is likely that the formation of endothelin-1 (1-31) and subsequent activation of endothelin ET(A) receptors are involved in the development of ocular hypertension induced by chymase.

摘要

糜酶是一种类胰凝乳蛋白酶的丝氨酸蛋白酶,仅储存于肥大细胞的分泌颗粒中,可将大内皮素转化为内皮素-1(1-31)。本研究的目的是评估糜酶对兔眼内压的影响。与对照组相比,注射糜酶(3和10 mU)导致眼内压有升高趋势,且在剂量为10 mU时眼内压显著升高。一种特异性糜酶抑制剂Suc-Val-Pro-Phe(P)(OPh)(2)可减轻糜酶诱导的高眼压。内皮素-1(1-31)也可引起高眼压,而选择性内皮素ET(A)受体拮抗剂环(D-天冬氨酸-脯氨酸-D-缬氨酸-亮氨酸-D-色氨酸)(BQ-123)可抑制这种高眼压。此外,BQ-123可抑制糜酶诱导的高眼压。这些结果表明,糜酶影响眼内压的调节,内皮素-1(1-31)的形成及随后内皮素ET(A)受体的激活可能参与了糜酶诱导的高眼压的发生。

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