11,12 -Epoxyeicosatrienoic acid (11,12 EET) reduces excitability and excitatory transmission in the hippocampus

Neuropharmacology
Nandkishor K MuleAnne Marowsky

Abstract

Recent studies suggest a role for the arachidonic acid-derived epoxyeicosatrienoic acids (EETs) in attenuating epileptic seizures. However, their effect on neurotransmission has never been investigated in detail. Here, we studied how 11,12- and 14,15 EET affect excitability and excitatory neurotransmission in mouse hippocampus. 11,12 EET (2 μM), but not 14,15 EET (2 μM), induced the opening of a hyperpolarizing K+ conductance in CA1 pyramidal cells. This action could be blocked by BaCl2, the G protein blocker GDPβ-S and the GIRK1/4 blocker tertiapin Q and the channel was thus identified as a GIRK channel. The 11,12 EET-mediated opening of this channel significantly reduced excitability of CA1 pyramidal cells, which could not be blocked by the functional antagonist EEZE (10 μM). Furthermore, both 11,12 EET and 14,15 EET reduced glutamate release on CA1 pyramidal cells with 14,15 EET being the less potent regioisomer. In CA1 pyramidal cells, 11,12 EET reduced the amplitude of excitatory postsynaptic currents (EPSCs) by 20% and the slope of field excitatory postsynaptic potentials (fEPSPs) by 50%, presumably via a presynaptic mechanism. EEZE increased both EPSC amplitude and fEPSP slope by 40%, also via a presynaptic mechanism, bu...Continue Reading

References

May 1, 1997·Stroke; a Journal of Cerebral Circulation·N J AlkayedD R Harder
Aug 29, 1998·Archives of Biochemistry and Biophysics·G LuoJ A Goldstein
Feb 3, 1999·Molecular Pharmacology·J ChenR L Rosenberg
Oct 18, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Gary D SnyderArthur A Spector
Dec 24, 2002·The Journal of Biological Chemistry·Celia P BriscoeAlison I Muir
Dec 14, 2004·European Journal of Pharmacology·Louise S HarringtonJane A Mitchell
Nov 5, 2005·Circulation Research·Scott EarleyJoseph E Brayden
Feb 16, 2006·The FEBS Journal·Mohammed Al-AnizyDavid R Bell
Feb 16, 2006·American Journal of Physiology. Renal Physiology·Mairéad A CarrollJohn C McGiff
Sep 22, 2006·American Journal of Physiology. Cell Physiology·Arthur A Spector, Andrew W Norris
Dec 8, 2006·Nature·Ed S LeinAllan R Jones
Dec 14, 2006·Prostaglandins & Other Lipid Mediators·Bora InceogluBruce D Hammock
Apr 19, 2007·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Wenri ZhangNabil J Alkayed
Apr 27, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ines P KoernerNabil J Alkayed
Jul 10, 2007·Journal of Medicinal Chemistry·Sung Hee HwangBruce D Hammock
Sep 18, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Ingrid FlemingRudi Busse
Oct 22, 2008·Nature Neuroscience·Rene O Sanchez-MejiaLennart Mucke
Jun 24, 2009·Prostaglandins & Other Lipid Mediators·Jeffrey J IliffNabil J Alkayed
Sep 19, 2009·The Journal of Pharmacology and Experimental Therapeutics·Yuenmu ChenWilliam B Campbell
Feb 9, 2010·Nature Neuroscience·Jennie L ConroyLindsay B Hough
May 1, 2010·Expert Opinion on Therapeutic Patents·Hong C Shen
Mar 2, 2011·Expert Reviews in Molecular Medicine·John D ImigDavid R Harder
May 4, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Marco SisignanoChristian Brenneis
Oct 9, 2012·Prostaglandins & Other Lipid Mediators·Rui LiDao Wen Wang
Jan 15, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Joan P GravesDarryl C Zeldin

❮ Previous
Next ❯

Citations

Apr 18, 2020·The Proceedings of the Nutrition Society·Mathieu Di MiceliSophie Layé
Jan 16, 2019·Journal of Molecular Neuroscience : MN·Qiong WuQuanzhong Chang
Nov 5, 2019·Frontiers in Pharmacology·Tabea Osthues, Marco Sisignano
Dec 12, 2020·Journal of Neurochemistry·Yizhen TangXinghuai Sun
Nov 20, 2020·Nutrients·Morteza SarparastKin Sing Stephen Lee
May 29, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Li WanYue Zhang
Oct 30, 2021·Journal of Neuroscience Research·Enes AkyuzYam Nath Paudel
Jan 20, 2021·CNS & Neurological Disorders Drug Targets·Fatima MaqoudDomenico Tricarico

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.