Tachykinins as enhancers of prostaglandin E2-induced intraocular inflammation.
The effects of tachykinins on prostaglandin E2 (PGE2)-induced intraocular inflammation were investigated. PGE2 (0.01% or 0.1%) instillation induced iridal hyperemia and protein leakage into the aqueous humor in rabbits, but caused minimal miosis. Intravitreally injected substance P (SP) or neurokinin A (NKA), on the other hand, did not induce protein leakage into the aqueous humor in normal rabbits, but they (SP 10 micrograms/eye or NKA 50 micrograms/eye) did induce long-lasting miosis. The miotic activity of SP was about fivefold stronger than that of NKA. Intravitreally injected SP (10 micrograms/eye) but not NKA (50 micrograms/eye) increased PGE2 concentration in the aqueous humor in normal rabbits. In addition, SP (10 micrograms/eye) or NKA (50 micrograms/eye) markedly enhanced protein leakage into the aqueous humor induced by PGE2 instillation. Pretreatment with indomethacin partially blocked the enhancing effect of SP on protein leakage, while it did not block that of NKA. These results suggest that SP or NKA may enhance intraocular inflammation in vivo. However, the mechanisms of these effects of SP and NKA may be different. The enhancing effect of SP in eye inflammation may be partially due to an increased turnover of arachidonic acid into PGE2 caused by activation of the enzyme cyclooxygenase.
Tsuji
F
F
Discovery Research Division, Santen Pharmaceutical Co., Ltd., Osaka, Japan.
Hamada
M
M
Shirasawa
E
E
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001082:Aqueous Humor / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D009877:Endophthalmitis / Q000139:chemically induced*; D005123:Eye / Q000187:drug effects; D005136:Eye Proteins / Q000378:metabolism; D006940:Hyperemia / Q000139:chemically induced; D007213:Indomethacin / Q000494:pharmacology; D007267:Injections; D007498:Iris / Q000098:blood supply; D008297:Male; D015877:Miosis; D015288:Neurokinin A / Q000494:pharmacology; D011817:Rabbits; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015320:Tachykinins / Q000502:physiology*; D014822:Vitreous Body / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005136:Eye Proteins; D015320:Tachykinins; D013373:Substance P; D015288:Neurokinin A; D015232:Dinoprostone; D007213:Indomethacin