Prostaglandin-like Activity in Ocular Inflammation

When rabbit chopped adipose tissue was incubated with a lipolytic agent (adrenocorticotrophic hormone, ACTH1–24, 0.1 μg/ml) in Krebs solution, prostaglandin E2 was formed in the tissue and about the same amount was found in the medium. In the presence of indomethacin (1 μg/ml) the appearance of prostaglandin E2 was almost abolished both in the tissue and in the medium. When the incubation was carried out in the presence of hydrocortisone or betamethasone (1–10 μg/ml) the concentration of prostaglandin E2 leaking or carried into the medium was significantly reduced, whereas that remaining in the tissue was significantly increased. This action of the steroids was not reversed by increasing substrate (arachidonic acid) concentration in the medium. The steroids did not affect lipolysis, nor did they influence prostaglandin metabolism since such activity was not detectable in the adipose tissue. Anti‐inflammatory steroids therefore did not reduce prostaglandin formation but increased the tissue/medium ratio, which supports the view that they inhibit the release of prostaglandins after these have been synthesized.

Section: Discussionmentioning

confidence: 96%

INHIBITION BY GLUCOCORTICOIDS OF PROSTAGLANDIN RELEASE FROM ADIPOSE TISSUE in vitro

Chang

Lewis

Piper

1977

“…Vasodilator effects are also reported (Starr, 1971;Whitelocke & Eakins, 1973). Prostaglandins have been implicated in inflammatory conditions of the eye such as uveitis (Eakins, Whitelocke, Bennett & Martenet, 1972; Eakins, Whitelocke, Perkins, Bennett & Unger, 1972) and it is. possible they are involved in glaucoma (Wyllie & Wyllie, 1971).…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin E₂ and the bovine sphincter pupillae

Posner

1973

Summary1. The bovine isolated sphincter pupillae incubated in Krebs solution releases a biologically active substance tentatively identified as prostaglandin E2. 2. The prostaglandin did not appear to be of neural origin or to result merely from tissue degeneration.3. The spontaneous release of prostaglandin E,-like material was related to the tone of the sphincter. Output increased as tone was acquired after setting up the tissue and fell when various procedures were used to reduce the tone. 4. Low concentrations of E and F-type prostaglandins produced slow, wellsustained contractions of the atonic sphincter, prostaglandin E2 being the most potent of those tested. The responses to prostaglandin EB were antagonized selectively by a prostaglandin antagonist SC-19220 (a dibenzoxazepine derivative) which in higher concentrations caused dose-dependent relaxations of the preparation. 5. Prostaglandins did not appear to modulate transmission from nerve to muscle in the sphincter. 6. The hypothesis that prostaglandin E2 might be produced to act as a local hormone causing tonic contraction of the sphincter pupillae is discussed.

“…These observations led to the suggestion that substances which inhibit the action or synthesis of prostaglandins might be of value as ocular anti-inflammatory agents (Eakins et al, 1972b).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the Prostaglandin Synthetase Systems in Ocular Tissues by Indomethacin

Bhattacherjee

Eakins

1974

100

We have compared the sensitivity of the prostaglandin synthetase systems derived from microsomal fractions of rabbit ocular tissues (anterior uvea, conjunctiva and retina) with other rabbit tissues such as the kidney medulla and spleen, to inhibition by indomethacin. Generation of prostaglandin‐like activity by the microsomal fractions from added arachidonic acid varied with the tissue used. Highest activity was found in the kidney medulla, then in descending order, the conjunctiva, anterior uvea, spleen, retina and cornea. Indomethacin was most potent in the spleen (ID50 0.045 μg/ml) then in decreasing order in the kidney medulla, conjunctiva, anterior uvea and weakest in the retina, where the ID50 for indomethacin was 50 μg/ml. The differential sensitivity to inhibition of the prostaglandin synthetase systems from different tissues is an important consideration in the development of new ocular anti‐inflammatory agents.