Effects of endothelin receptor antagonists on anterior chamber inflammation induced by intravitreal injection of endothelin-1.
To investigate the role of endothelin receptors (ET(A) and ET(B)) in the inflammatory reaction induced by endothelin-1 (ET-1), the time course of changes in aqueous protein concentration (APC) after the intravitreal injection of ET-1 (10(-4), 10(-5) M) was measured using a laser flare-cell meter in pigmented rabbit eyes. The effects of pre-treatment with specific ET(A) receptor antagonist (97-139) (10(-1), 10(-2), 10(-3), 10(-4) M), specific ET(B) receptor antagonist (BQ-788) (1.6 x 10(-3) M), and vehicle solution were assessed. The influence of ET(A)receptor antagonist pre-treatment on aqueous prostaglandin E(2) and leukotriene B(4) concentrations was also evaluated. As a result, pre-treatment with ET(A) receptor antagonist blocked the APC increase induced by 10(-4) M ET-1 in a dose dependent fashion, while BQ-788 did not suppress the inflammatory reaction. The injection of ET-1 increased aqueous prostaglandin E(2) concentration, which was inhibited by pre-treatment with ET(A) receptor antagonist. Aqueous leukotriene B(4) concentration was not affected by ET-1 nor ET(A) receptor antagonist. In conclusion, ET(A) receptor mediates the increases in aqueous protein and prostaglandin E(2) concentration induced by ET-1 injection, and this inflammatory reaction occurs via the cyclooxygenase pathway of arachidonic acid cascade.
Shoji
N
N
Department of Ophthalmology, University of Kitasato School of Medicine, Kanagawa, 228-0055, Japan.
Oshika
T
T
Amano
S
S
Masuda
K
K
D000818:Animals; D002109:Caffeic Acids / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000633:toxicity*; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011817:Rabbits; D017466:Receptors, Endothelin / Q000502:physiology; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control
D002109:Caffeic Acids; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D005136:Eye Proteins; D009842:Oligopeptides; D010880:Piperidines; D017466:Receptors, Endothelin; C086421:S 0139; D007975:Leukotriene B4; C086539:BQ 788; D009828:Oleanolic Acid; D015232:Dinoprostone