Konno Takashi, Maruichi Midori, Takai Shinji, Oku Hidehiro, Sugiyama Tetsuya, Uchibori Takehiro, Nagai Akihiko, Kogi Kentaro, Ikeda Tsunehiko, Miyazaki Mizuo
Drug Research Section II, Fukushima Research Laboratories, Yuno, Iizaka-machi, Fukushima City, Fukushima, Japan.
Eur J Pharmacol. 2005 Nov 7;524(1-3):132-7. doi: 10.1016/j.ejphar.2005.09.048. Epub 2005 Oct 25.
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.
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。