Role of prostanoid production and receptors in the regulation of retinal endogenous amino acid neurotransmitters by 8-isoprostaglandin E2, ex vivo.
The role of enzymes and receptors of the prostanoid pathway in the inhibitory effect of 8-isoprostaglandin E2 (8-isoPGE2) on endogenous amino acid neurotransmitter levels was examined, ex vivo. Freshly isolated bovine eyeballs were injected intravitreally with IsoPs, incubated in Krebs buffer for 30 min and retina prepared for HPLC-ECD detection of amino acids. 8-isoPGE2 attenuated retinal glutamate and its metabolite, glutamine and glycine in a concentration-dependent manner. The nonselective cyclooxygenase (COX)-inhibitor, flurbiprofen, COX-2 selective inhibitor, NS-398 and thromboxane (Tx) synthase inhibitor, furegrelate had no effect on both basal amino acid levels and the inhibitory effects of 8-isoPGE2 (1-100 μM) on the retinal amino acids. Whereas the TP-receptor antagonist SQ-29548(10 μM) exhibited no effect, SC-19220(EP1; 30 μM), AH-6809(EP(1-3); 30 μM) and AH-23848(EP4; 30 μM) reversed the inhibitory effects of 8-isoPGE2 (0.01-100 μM) on glutamate, glutamine and glycine levels. We conclude that prostanoid EP-receptors regulate the inhibitory effect of 8-isoPGE2 on basal levels of endogenous amino acids in bovine retina, ex vivo.
Zhao
Min
M
Department of Pharmacy Sciences, Creighton University, 2500 California Plaza, Omaha, NE 6878, USA. zhaom@unmc.edu
Destache
Christopher J
CJ
Ohia
Sunny E
SE
Opere
Catherine A
CA
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002417:Cattle; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D005480:Flurbiprofen / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism*; D006834:Hydrazines / Q000494:pharmacology; D028421:Isoprostanes / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009578:Nitrobenzenes / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000502:physiology*; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D044004:Xanthones / Q000494:pharmacology
D001572:Benzofurans; D001713:Biphenyl Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D028421:Isoprostanes; D018377:Neurotransmitter Agents; D009578:Nitrobenzenes; D011453:Prostaglandins; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; D044004:Xanthones; D005973:Glutamine; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D018698:Glutamic Acid; D005480:Flurbiprofen; C046926:AH 23848; C045749:SQ 29548; D015232:Dinoprostone; C039936:furegrelate; D005998:Glycine; C011987:8-isoprostaglandin E2