title: Regulation of [³H]d-aspartate release by the 5-F(2t)-isoprostane and its 5-epimer in isolated bovine retina.
abstract: We have evidence that 15-F₂-isoprostanes (15-F₂-IsoPs) regulate excitatory neurotransmitter release in ocular tissues. Although 5-F₂-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-F₂-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; IC₂₅ = 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 (IC₂₅ value of 3 nM). Although the prostanoid-receptor antagonists, AH 6809 (10 μM; EP₁₋₃/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; EP₁) 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; EP₁ and AH 23848 (1 μM; EP₄) reversed the inhibitory action elicited by 5-epi-5-F(2t)-IsoP (0.1 μM) on the neurotransmitter release. We conclude that the 5-F₂-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.
authors.affiliation: Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University Medical Center, 2500 California Plaza, Omaha, NE 68178, USA.
authors.forename: Jamal
authors.initials: J
authors.lastname: Jamil
authors.forename: Ashley
authors.initials: A
authors.lastname: Wright
authors.forename: Na'cara
authors.initials: N
authors.lastname: Harrison
authors.forename: Edem
authors.initials: E
authors.lastname: Kegey
authors.forename: Arnecia Faye
authors.initials: AF
authors.lastname: Flowers
authors.forename: Namonique Jarell
authors.initials: NJ
authors.lastname: Flyod
authors.forename: Casey
authors.initials: C
authors.lastname: Kotera
authors.forename: Alexandre
authors.initials: A
authors.lastname: Guy
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Galano
authors.forename: Thierry
authors.initials: T
authors.lastname: Durand
authors.forename: Ya Fatou
authors.initials: YF
authors.lastname: Njie-Mbye
authors.forename: Sunny E
authors.initials: SE
authors.lastname: Ohia
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Opere
mesh_terms: D000818:Animals; D002417:Cattle; D026603:D-Aspartic Acid / Q000378:metabolism*; D028441:F2-Isoprostanes / Q000378:metabolism*; D066298:In Vitro Techniques; D012160:Retina / Q000378:metabolism*; D014316:Tritium
chemical_list: C463000:5-F(2t)-isoprostane; D028441:F2-Isoprostanes; D014316:Tritium; D026603:D-Aspartic Acid
references.citation: J Pharmacol Exp Ther. 1997 Sep;282(3):1198-205
references.pmid: 9316826
references.citation: Br J Pharmacol. 1996 Jul;118(5):1285-93
references.pmid: 8818355
references.citation: Eye (Lond). 2008 Apr;22(4):582-9
references.pmid: 17948040
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2006 Aug;373(5):367-75
references.pmid: 16738877
references.citation: Eur J Pharmacol. 1987 Oct 27;142(3):409-17
references.pmid: 3428354
references.citation: Gastroenterology. 1997 Jan;112(1):208-13
references.pmid: 8978361
references.citation: Proc Natl Acad Sci U S A. 1990 Dec;87(23):9383-7
references.pmid: 2123555
references.citation: J Ocul Pharmacol Ther. 2004 Dec;20(6):489-508
references.pmid: 15684809
references.citation: Biochem Pharmacol. 1995 Nov 9;50(10):1731-3
references.pmid: 7503778
references.citation: J Neurosci Res. 1986;15(2):205-16
references.pmid: 2870197
references.citation: J Pharmacol Exp Ther. 2003 Apr;305(1):347-52
references.pmid: 12649388
references.citation: J Biol Chem. 1996 Apr 12;271(15):8919-24
references.pmid: 8621535
references.citation: FASEB J. 1999 Jun;13(9):1025-30
references.pmid: 10336884
references.citation: Neurochem Res. 2008 Jan;33(1):37-42
references.pmid: 17674205
references.citation: Invest Ophthalmol Vis Sci. 2002 May;43(5):1475-87
references.pmid: 11980863
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Jun;280(6):L1067-82
references.pmid: 11350785
references.citation: Am J Physiol. 1998 May;274(5):R1406-16
references.pmid: 9612409
references.citation: Free Radic Res. 2001 Sep;35(3):257-64
references.pmid: 11697124
references.citation: Methods Mol Biol. 1999;120:257-85
references.pmid: 10343322
references.citation: Methods Find Exp Clin Pharmacol. 2008 Nov;30(9):697-701
references.pmid: 19229378
references.citation: Arch Ophthalmol. 1998 Sep;116(9):1213-6
references.pmid: 9747682
references.citation: Neurochem Res. 2005 Jan;30(1):129-37
references.pmid: 15756941
references.citation: Angew Chem Int Ed Engl. 2008;47(32):5894-955
references.pmid: 18649300
references.citation: Br J Pharmacol. 1996 Nov;119(6):1276-80
references.pmid: 8937734
references.citation: Bioorg Med Chem Lett. 2001 Sep 17;11(18):2495-8
references.pmid: 11549454
references.citation: Neurochem Res. 2000 Apr;25(4):491-6
references.pmid: 10823581
references.citation: Br J Ophthalmol. 2003 Mar;87(3):353-6
references.pmid: 12598453
references.citation: Prostaglandins Leukot Essent Fatty Acids. 1998 Dec;59(6):349-55
references.pmid: 10102379
references.citation: J Neurosci Res. 2005 Dec 1;82(5):674-89
references.pmid: 16273539
references.citation: Free Radic Biol Med. 2004 Jan 15;36(2):163-72
references.pmid: 14744628
references.citation: J Pharmacol Exp Ther. 2002 Jun;301(3):1060-6
references.pmid: 12023538
references.citation: Br J Pharmacol. 2002 Mar;135(5):1276-80
references.pmid: 11877336
references.citation: J Biol Chem. 1995 Apr 28;270(17):9800-8
references.pmid: 7730359
references.citation: Vision Res. 1997 Dec;37(24):3483-93
references.pmid: 9425525
references.citation: Mol Vis. 2002 Mar 13;8:51-8
references.pmid: 11951086
references.citation: Adv Prostaglandin Thromboxane Leukot Res. 1995;23:237-9
references.pmid: 7732843
references.citation: Am J Respir Cell Mol Biol. 2008 Feb;38(2):143-52
references.pmid: 17690331
references.citation: Exp Eye Res. 2009 Oct;89(4):532-7
references.pmid: 19523949
references.citation: Rev Med Interne. 2000 Mar;21(3):304-7
references.pmid: 10763198
references.citation: Surv Ophthalmol. 1997 Feb;41 Suppl 2:S47-52
references.pmid: 9154276
references.citation: Neurosci Lett. 2006 May 1;398(1-2):63-8
references.pmid: 16442231
references.citation: Br J Pharmacol. 2000 Aug;130(8):1903-10
references.pmid: 10952681
references.citation: Br J Pharmacol. 2004 Feb;141(4):600-9
references.pmid: 14744812
references.citation: Biochem Biophys Res Commun. 1997 Apr 28;233(3):668-72
references.pmid: 9168911
references.citation: Mol Pharmacol. 2001 Jun;59(6):1446-56
references.pmid: 11353805
references.citation: Biochim Biophys Acta. 2000 Jan 17;1483(2):285-93
references.pmid: 10634944
references.citation: Neurochem Res. 2009 Dec;34(12):2170-80
references.pmid: 19513831
references.citation: Mol Vis. 2007 Feb 07;13:190-5
references.pmid: 17327824
references.citation: Free Radic Biol Med. 2005 Mar 15;38(6):698-710
references.pmid: 15721980
references.citation: Stroke. 2000 Feb;31(2):516-24; discussion 525
references.pmid: 10657431
references.citation: Surv Ophthalmol. 2002 Aug;47 Suppl 1:S13-33
references.pmid: 12204698
references.citation: Neurochem Res. 1996 Mar;21(3):361-8
references.pmid: 9139243
references.citation: Neurochem Res. 2000 Jun;25(6):853-60
references.pmid: 10944004
references.citation: Curr Eye Res. 2004 May;28(5):367-72
references.pmid: 15287374
references.citation: Ophthalmic Res. 2000 Jul-Aug;32(4):133-7
references.pmid: 10828732
references.citation: Am J Physiol. 1993 Jun;264(6 Pt 1):C1619-24
references.pmid: 8333509
references.citation: Invest Ophthalmol Vis Sci. 2004 Mar;45(3):892-9
references.pmid: 14985307
references.citation: Br J Pharmacol. 1991 Nov;104(3):585-90
references.pmid: 1839139
references.citation: Eur J Pharmacol. 2003 May 30;470(1-2):73-8
references.pmid: 12787833
references.citation: Am J Respir Crit Care Med. 1996 Feb;153(2):590-6
references.pmid: 8564103
references.citation: Invest Ophthalmol Vis Sci. 1998 May;39(6):972-81
references.pmid: 9579476
references.citation: Free Radic Biol Med. 1997;23(6):943-54
references.pmid: 9378374