Inhibition of cyclooxygenase-2, but not cyclooxygenase-1, reduces prostaglandin E2 secretion from diabetic rat retinas.
Up-regulation of cyclooxygenase-2 occurs in retinal cells during the early onset of diabetic retinopathy. Under these conditions, prostaglandin production is elevated, which in turn leads to an increased expression of vascular endothelial growth factor (VEGF)--a growth factor implicated in vascular leakage and neovascularization. In this ex vivo study, we tested whether cyclooxygenase-1 or cyclooxygenase-2 is responsible for diabetes-induced secretion of prostaglandin E2 from isolated rat retinas. Celecoxib, a selective cyclooxygenase-2 inhibitor, significantly inhibited prostaglandin E2 secretion, whereas SC560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole], a selective cyclooxygenase-1 inhibitor, had no inhibitory effect. These results suggests that the enzymatic activity of cyclooxygenase-2, but not cyclooxygenase-1, results in prostaglandin E2 secretion under diabetic conditions.
Ayalasomayajula
Surya P
SP
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 985840 Nebraska Medical Center, Omaha, NE 68198-5840, USA.
Amrite
Aniruddha C
AC
Kompella
Uday B
UB
D000818:Animals; D000068579:Celecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003930:Diabetic Retinopathy / Q000209:etiology / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D066298:In Vitro Techniques; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D000068579:Celecoxib; D015232:Dinoprostone