TY - JOUR
T1 - Regulation of [ 3H]D-aspartate release by the 5-F 2t-isoprostane and its 5-epimer in isolated bovine retina
AU - Jamil, Jamal
AU - Wright, Ashley
AU - Harrison, Na'Cara
AU - Kegey, Edem
AU - Flowers, Arnecia Faye
AU - Flyod, Namonique Jarell
AU - Kotera, Casey
AU - Guy, Alexandre
AU - Galano, Jean Marie
AU - Durand, Thierry
AU - Njie-Mbye, Ya Fatou
AU - Ohia, Sunny E.
AU - Opere, Catherine A.
PY - 2012/3/1
Y1 - 2012/3/1
N2 - 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.
AB - 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.
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U2 - 10.1007/s11064-011-0645-5
DO - 10.1007/s11064-011-0645-5
M3 - Article
C2 - 22081406
AN - SCOPUS:84862845961
VL - 37
SP - 574
EP - 582
JO - Neurochemical Research
JF - Neurochemical Research
SN - 0364-3190
IS - 3
ER -