Arachidonic acid metabolites and peroxide-induced inhibition of [3H]D-aspartate release from bovine isolated retinae.
We have previously shown that hydrogen peroxide (H2O2) can inhibit K+-depolarization-evoked [3H]D-aspartate release from bovine isolated retinae. In the present study, we investigated the role of arachidonic acid metabolites in the inhibitory response elicited by H2O2 in the bovine retinae. Furthermore, we examined the direct effect of H2O2 on the production of prostaglandins and isoprostanes in this tissue. Isolated bovine retinae were prepared for studies of [3H]D-aspartate release using the Superfusion Method. Release of [3H]D-aspartate was elicited by Krebs solution containing an iso-osmotic concentration of KCl (50 mM). A direct action of H2O2 on prostaglandin E2 (PGE2) and 8-isoprostane F2alpha (8-iso-PGF2alpha) was also measured by enzyme-linked immunosorbant assay (ELISA). The cyclooxygenase inhibitor, flurbiprofen (3 microM), or the thromboxane-receptor antagonist, SQ 29548 (10 microM) had no significant (p > 0.05) effect on K+-evoked [3H]D-aspartate release. On the other hand, both flurbiprofen (3 microM) and SQ 29548 (10 microM) blocked the inhibition of K+-evoked [3H]D-aspartate induced by H2O2 (30 microM). In concentrations up to 100 microM, H2O2 caused an increase in PGE2 and 8-iso-PGF2alpha over basal levels. For instance, H2O2 (100 microM) increased PGE2 and 8-iso-PGF2alpha over basal levels by 348 +/- 41% and 185 +/- 26 (n = 4), respectively. We conclude that the peroxide-mediated inhibition of [3H]D-aspartate may involve the production of prostaglandins and isoprostanes in the bovine isolated retinae.
Department of Pharmacy Sciences, School of Pharmacy and Allied Health Professions, Creighton University, Omaha, NE, USA.
Angela M
AM
LeDay
Kaustubh H
KH
Kulkarni
Catherine A
CA
Opere
Sunny E
SE
Ohia
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002417:Cattle; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D026603:D-Aspartic Acid / Q000378:metabolism*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005231:Fatty Acids, Unsaturated; D005480:Flurbiprofen / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D012160:Retina / Q000187:drug effects* / Q000378:metabolism
D001095:Arachidonic Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D017482:Receptors, Thromboxane; C075750:8-epi-prostaglandin F2alpha; D026603:D-Aspartic Acid; D005480:Flurbiprofen; D011189:Potassium Chloride; C045749:SQ 29548; D015237:Dinoprost; D006861:Hydrogen Peroxide; D015232:Dinoprostone