Effect of chymase on intraocular pressure in rabbits.
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.
Konno
Takashi
T
Drug Research Section II, Fukushima Research Laboratories, Yuno, Iizaka-machi, Fukushima City, Fukushima, Japan. konno.takashi@toaeiyo.co.jp
Maruichi
Midori
M
Takai
Shinji
S
Oku
Hidehiro
H
Sugiyama
Tetsuya
T
Uchibori
Takehiro
T
Nagai
Akihiko
A
Kogi
Kentaro
K
Ikeda
Tsunehiko
T
Miyazaki
Mizuo
M
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D053818:Chymases; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000008:administration & dosage / Q000031:analogs & derivatives; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage; D010456:Peptides, Cyclic / Q000494:pharmacology; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage; D012697:Serine Endopeptidases / Q000008:administration & dosage* / Q000235:genetics; D013997:Time Factors
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011994:Recombinant Proteins; C114932:endothelin-1 (1-31); C102024:succinyl-valyl-prolyl-phenylalanyl-diphenylphosphonate; D012697:Serine Endopeptidases; D053818:Chymases; C072247:cyclo(Trp-Asp-Pro-Val-Leu)