s-0139 and Uveitis--Anterior

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.

Topics: Animals; Caffeic Acids; Dinoprostone; Endothelin Receptor Antagonists; Endothelin-1; Eye Proteins; Female; Leukotriene B4; Male; Oleanolic Acid; Oligopeptides; Piperidines; Rabbits; Receptors, Endothelin; Uveitis, Anterior