Regulation of [ 3H]D-aspartate release by the 5-F 2t-isoprostane and its 5-epimer in isolated bovine retina

Jamal Jamil, Ashley Wright, Na'Cara Harrison, Edem Kegey, Arnecia Faye Flowers, Namonique Jarell Flyod, Casey Kotera, Alexandre Guy, Jean Marie Galano, Thierry Durand, Ya Fatou Njie-Mbye, Sunny E. Ohia, Catherine A. Opere

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

We have evidence that 15-F 2-isoprostanes (15-F 2-IsoPs) regulate excitatory neurotransmitter release in ocular tissues. Although 5-F 2-IsoPs are abundantly produced in mammals, their pharmacological actions on neurotransmitter release remain unknown. In the present study, we compared the effect of the 5-F 2-IsoP epimer pair, 5-F 2t-IsoP (C5-OH in β-position) and 5-epi-5-F 2t-IsoP (C5-OH in α-position), on K +-evoked [ 3H]D-aspartate release in isolated bovine retina. We further examined the role of prostanoid receptors on the inhibitory action of 5-epi-5-F 2t-IsoP on [ 3H]D-aspartate overflow. Isolated bovine retina were prepared for studies of K +-evoked release of [ 3H]D-aspartate using the superfusion method. 5-epi-5-F 2t-IsoP (0.01 nM to 1 μM), attenuated K +-evoked [ 3H]D-aspartate release in a concentration-dependent manner, with the inhibitory effect of 26.9% (P <0.001; IC 25 = 0.2 μM) being achieved at 1 μM concentration. Its 5-(S)-OH-epimer, 5-F 2t-IsoP (0.1 nM-1 μM), exhibited an inhibitory biphasic action, yielding a maximal response of 35.7% (P <0.001) at 10 nM concentration of the drug (IC 25 value of 3 nM). Although the prostanoid-receptor antagonists, AH 6809 (10 μM; EP 1-3/DP) and BAY-u3405 (10 μM; DP/Tx) exhibited no effect on 5-epi-5-F 2t-IsoP (10 nM-1 μM)-mediated inhibition, SC-19220 (1 μM; EP 1) completely reversed 5-epi-5-F 2t-IsoP (0.1 μM and 1 μM)- induced attenuation of K +-evoked [ 3H]D-aspartate release. Similarly, both SC-51322 (10 μM; EP 1) and AH 23848 (1 μM; EP 4) reversed the inhibitory action elicited by 5-epi-5-F 2t-IsoP (0.1 μM) on the neurotransmitter release. We conclude that the 5-F 2-IsoP epimer pair, 5-F 2t-IsoP and 5-epi-5-F 2t-IsoP, attenuate K +-induced [ 3H]D-aspartate release in isolated bovine retina presumably via prostanoid receptor dependent mechanisms. The trans-orientation of the allylic hydroxyl group at position C5 accounts for the apparent biphasic response exhibited by 5-F 2t-IsoP on excitatory neurotransmitter release.

Original languageEnglish (US)
Pages (from-to)574-582
Number of pages9
JournalNeurochemical Research
Volume37
Issue number3
DOIs
StatePublished - Mar 1 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

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