Role of the Non-enzymatic Metabolite of Eicosapentaenoic Acid, 5-epi-5-F3t-Isoprostane in the Regulation of [3H]d-Aspartate Release in Isolated Bovine Retina

Jamal Jamil, Pratik Bankhele, Ankita Salvi, Jaimee E. Mannix, Camille Oger, Alexandre Guy, Jean Marie Galano, Thierry Durand, Ya Fatou Njie-Mbye, Sunny E. Ohia, Catherine A. Opere

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

We have evidence that F2-isoprostanes (F2-IsoPs) regulate the release of excitatory neurotransmitters in isolated bovine retina. Although 5-F3-IsoPs are generated in mammals, in vivo, their pharmacological actions on neurotransmitter release remain unknown. In this study, we investigated the effect of 5-epi-5-F3t-IsoP on K+-evoked [3H]d-aspartate release in isolated bovine retina using the superfusion method. Furthermore, we examined the role of arachidonic acid metabolites in the regulation of the neurotransmitter release by this novel IsoP. In the concentration range, 0.01 nM–0.1 µM, 5-epi-5-F3t-IsoP inhibited K+-evoked [3H]d-aspartate release in a concentration-dependent manner, achieving a maximum inhibition of 46.9 % at 0.1 µM (IC30 = 1 nM). The prostanoid receptor antagonists, AH 6809 (EP1–3/DP; 10 µM), SC 51322 (EP1; 10 µM) and SC 19220 (EP1; 1 µM) partially reversed 5-epi-5-F3t-IsoP-mediated inhibition of K+-induced [3H]d-aspartate release. Pretreatment of retinal tissues with the cyclooxygenase (COX) inhibitor, flurbiprofen (3 μM) unmasked a biphasic action of 5-epi-5-F3t-IsoP that was inhibitory at lower (0.1–10 pM) and stimulatory at higher concentrations (≥0.1 nM). The prostanoid pathway antagonists, BAY-u3405 (10 μM; TP/DP-receptors), SQ 29548 (10 μM; TP-receptor) and ozagrel (10 μM; Tx-synthase inhibitor) abolished the stimulatory action of the 5-epi-5-F3t-IsoP (0.1 μM) on neurotransmitter release. In conclusion, 5-epi-5-F3t-IsoP attenuates K+-induced [3H]d-aspartate release in a concentration-dependent manner by mechanisms that are partially dependent on activation of pre-junctional prostanoid EP1-receptors. Moreover, blockade of the COX-pathway unmasks a biphasic action for 5-epi-5-F3t-IsoP that is inhibitory at low concentrations and stimulatory at higher concentrations. Products of the thromboxane synthase pathway may partially account for the stimulatory action of this F3-IsoP on isolated bovine retina.

Original languageEnglish
Pages (from-to)2360-2369
Number of pages10
JournalNeurochemical Research
Volume39
Issue number12
DOIs
StatePublished - Nov 25 2014

Fingerprint

Isoprostanes
Eicosapentaenoic Acid
Metabolites
Aspartic Acid
Neurotransmitter Agents
Retina
Prostaglandins
Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide
Receptors, Prostaglandin E, EP1 Subtype
F2-Isoprostanes
Thromboxane Receptors
Flurbiprofen
Mammals
Cyclooxygenase Inhibitors
Thromboxanes
Prostaglandin-Endoperoxide Synthases
Arachidonic Acid
Chemical activation
Pharmacology
Tissue

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Biochemistry
  • Medicine(all)

Cite this

Role of the Non-enzymatic Metabolite of Eicosapentaenoic Acid, 5-epi-5-F3t-Isoprostane in the Regulation of [3H]d-Aspartate Release in Isolated Bovine Retina. / Jamil, Jamal; Bankhele, Pratik; Salvi, Ankita; Mannix, Jaimee E.; Oger, Camille; Guy, Alexandre; Galano, Jean Marie; Durand, Thierry; Njie-Mbye, Ya Fatou; Ohia, Sunny E.; Opere, Catherine A.

In: Neurochemical Research, Vol. 39, No. 12, 25.11.2014, p. 2360-2369.

Research output: Contribution to journalArticle

Jamil, Jamal ; Bankhele, Pratik ; Salvi, Ankita ; Mannix, Jaimee E. ; Oger, Camille ; Guy, Alexandre ; Galano, Jean Marie ; Durand, Thierry ; Njie-Mbye, Ya Fatou ; Ohia, Sunny E. ; Opere, Catherine A. / Role of the Non-enzymatic Metabolite of Eicosapentaenoic Acid, 5-epi-5-F3t-Isoprostane in the Regulation of [3H]d-Aspartate Release in Isolated Bovine Retina. In: Neurochemical Research. 2014 ; Vol. 39, No. 12. pp. 2360-2369.
@article{627f4e40c08c44e49641c8963830b462,
title = "Role of the Non-enzymatic Metabolite of Eicosapentaenoic Acid, 5-epi-5-F3t-Isoprostane in the Regulation of [3H]d-Aspartate Release in Isolated Bovine Retina",
abstract = "We have evidence that F2-isoprostanes (F2-IsoPs) regulate the release of excitatory neurotransmitters in isolated bovine retina. Although 5-F3-IsoPs are generated in mammals, in vivo, their pharmacological actions on neurotransmitter release remain unknown. In this study, we investigated the effect of 5-epi-5-F3t-IsoP on K+-evoked [3H]d-aspartate release in isolated bovine retina using the superfusion method. Furthermore, we examined the role of arachidonic acid metabolites in the regulation of the neurotransmitter release by this novel IsoP. In the concentration range, 0.01 nM–0.1 µM, 5-epi-5-F3t-IsoP inhibited K+-evoked [3H]d-aspartate release in a concentration-dependent manner, achieving a maximum inhibition of 46.9 {\%} at 0.1 µM (IC30 = 1 nM). The prostanoid receptor antagonists, AH 6809 (EP1–3/DP; 10 µM), SC 51322 (EP1; 10 µM) and SC 19220 (EP1; 1 µM) partially reversed 5-epi-5-F3t-IsoP-mediated inhibition of K+-induced [3H]d-aspartate release. Pretreatment of retinal tissues with the cyclooxygenase (COX) inhibitor, flurbiprofen (3 μM) unmasked a biphasic action of 5-epi-5-F3t-IsoP that was inhibitory at lower (0.1–10 pM) and stimulatory at higher concentrations (≥0.1 nM). The prostanoid pathway antagonists, BAY-u3405 (10 μM; TP/DP-receptors), SQ 29548 (10 μM; TP-receptor) and ozagrel (10 μM; Tx-synthase inhibitor) abolished the stimulatory action of the 5-epi-5-F3t-IsoP (0.1 μM) on neurotransmitter release. In conclusion, 5-epi-5-F3t-IsoP attenuates K+-induced [3H]d-aspartate release in a concentration-dependent manner by mechanisms that are partially dependent on activation of pre-junctional prostanoid EP1-receptors. Moreover, blockade of the COX-pathway unmasks a biphasic action for 5-epi-5-F3t-IsoP that is inhibitory at low concentrations and stimulatory at higher concentrations. Products of the thromboxane synthase pathway may partially account for the stimulatory action of this F3-IsoP on isolated bovine retina.",
author = "Jamal Jamil and Pratik Bankhele and Ankita Salvi and Mannix, {Jaimee E.} and Camille Oger and Alexandre Guy and Galano, {Jean Marie} and Thierry Durand and Njie-Mbye, {Ya Fatou} and Ohia, {Sunny E.} and Opere, {Catherine A.}",
year = "2014",
month = "11",
day = "25",
doi = "10.1007/s11064-014-1436-6",
language = "English",
volume = "39",
pages = "2360--2369",
journal = "Neurochemical Research",
issn = "0364-3190",
publisher = "Springer New York",
number = "12",

}

TY - JOUR

T1 - Role of the Non-enzymatic Metabolite of Eicosapentaenoic Acid, 5-epi-5-F3t-Isoprostane in the Regulation of [3H]d-Aspartate Release in Isolated Bovine Retina

AU - Jamil, Jamal

AU - Bankhele, Pratik

AU - Salvi, Ankita

AU - Mannix, Jaimee E.

AU - Oger, Camille

AU - Guy, Alexandre

AU - Galano, Jean Marie

AU - Durand, Thierry

AU - Njie-Mbye, Ya Fatou

AU - Ohia, Sunny E.

AU - Opere, Catherine A.

PY - 2014/11/25

Y1 - 2014/11/25

N2 - We have evidence that F2-isoprostanes (F2-IsoPs) regulate the release of excitatory neurotransmitters in isolated bovine retina. Although 5-F3-IsoPs are generated in mammals, in vivo, their pharmacological actions on neurotransmitter release remain unknown. In this study, we investigated the effect of 5-epi-5-F3t-IsoP on K+-evoked [3H]d-aspartate release in isolated bovine retina using the superfusion method. Furthermore, we examined the role of arachidonic acid metabolites in the regulation of the neurotransmitter release by this novel IsoP. In the concentration range, 0.01 nM–0.1 µM, 5-epi-5-F3t-IsoP inhibited K+-evoked [3H]d-aspartate release in a concentration-dependent manner, achieving a maximum inhibition of 46.9 % at 0.1 µM (IC30 = 1 nM). The prostanoid receptor antagonists, AH 6809 (EP1–3/DP; 10 µM), SC 51322 (EP1; 10 µM) and SC 19220 (EP1; 1 µM) partially reversed 5-epi-5-F3t-IsoP-mediated inhibition of K+-induced [3H]d-aspartate release. Pretreatment of retinal tissues with the cyclooxygenase (COX) inhibitor, flurbiprofen (3 μM) unmasked a biphasic action of 5-epi-5-F3t-IsoP that was inhibitory at lower (0.1–10 pM) and stimulatory at higher concentrations (≥0.1 nM). The prostanoid pathway antagonists, BAY-u3405 (10 μM; TP/DP-receptors), SQ 29548 (10 μM; TP-receptor) and ozagrel (10 μM; Tx-synthase inhibitor) abolished the stimulatory action of the 5-epi-5-F3t-IsoP (0.1 μM) on neurotransmitter release. In conclusion, 5-epi-5-F3t-IsoP attenuates K+-induced [3H]d-aspartate release in a concentration-dependent manner by mechanisms that are partially dependent on activation of pre-junctional prostanoid EP1-receptors. Moreover, blockade of the COX-pathway unmasks a biphasic action for 5-epi-5-F3t-IsoP that is inhibitory at low concentrations and stimulatory at higher concentrations. Products of the thromboxane synthase pathway may partially account for the stimulatory action of this F3-IsoP on isolated bovine retina.

AB - We have evidence that F2-isoprostanes (F2-IsoPs) regulate the release of excitatory neurotransmitters in isolated bovine retina. Although 5-F3-IsoPs are generated in mammals, in vivo, their pharmacological actions on neurotransmitter release remain unknown. In this study, we investigated the effect of 5-epi-5-F3t-IsoP on K+-evoked [3H]d-aspartate release in isolated bovine retina using the superfusion method. Furthermore, we examined the role of arachidonic acid metabolites in the regulation of the neurotransmitter release by this novel IsoP. In the concentration range, 0.01 nM–0.1 µM, 5-epi-5-F3t-IsoP inhibited K+-evoked [3H]d-aspartate release in a concentration-dependent manner, achieving a maximum inhibition of 46.9 % at 0.1 µM (IC30 = 1 nM). The prostanoid receptor antagonists, AH 6809 (EP1–3/DP; 10 µM), SC 51322 (EP1; 10 µM) and SC 19220 (EP1; 1 µM) partially reversed 5-epi-5-F3t-IsoP-mediated inhibition of K+-induced [3H]d-aspartate release. Pretreatment of retinal tissues with the cyclooxygenase (COX) inhibitor, flurbiprofen (3 μM) unmasked a biphasic action of 5-epi-5-F3t-IsoP that was inhibitory at lower (0.1–10 pM) and stimulatory at higher concentrations (≥0.1 nM). The prostanoid pathway antagonists, BAY-u3405 (10 μM; TP/DP-receptors), SQ 29548 (10 μM; TP-receptor) and ozagrel (10 μM; Tx-synthase inhibitor) abolished the stimulatory action of the 5-epi-5-F3t-IsoP (0.1 μM) on neurotransmitter release. In conclusion, 5-epi-5-F3t-IsoP attenuates K+-induced [3H]d-aspartate release in a concentration-dependent manner by mechanisms that are partially dependent on activation of pre-junctional prostanoid EP1-receptors. Moreover, blockade of the COX-pathway unmasks a biphasic action for 5-epi-5-F3t-IsoP that is inhibitory at low concentrations and stimulatory at higher concentrations. Products of the thromboxane synthase pathway may partially account for the stimulatory action of this F3-IsoP on isolated bovine retina.

UR - http://www.scopus.com/inward/record.url?scp=84912521130&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84912521130&partnerID=8YFLogxK

U2 - 10.1007/s11064-014-1436-6

DO - 10.1007/s11064-014-1436-6

M3 - Article

VL - 39

SP - 2360

EP - 2369

JO - Neurochemical Research

JF - Neurochemical Research

SN - 0364-3190

IS - 12

ER -