alpha1beta2delta, a silent GABAA receptor: recruitment by tracazolate and neurosteroids.

British Journal of Pharmacology
N ZheleznovaD S Weiss

Abstract

This study investigated the alpha(1)beta(2)delta isoform of the GABA(A) receptor that is presumably expressed in the forebrain. The functional and pharmacological properties of this receptor combination are largely unknown. We expressed alpha(1)beta(2)delta GABA(A) receptors in Xenopus laevis oocytes. GABA-activated currents, in the presence and absence of modulators, were recorded using the two-electrode voltage clamp technique. The alpha(1)beta(2)delta isoform of the GABA(A) receptor exhibited an extremely small GABA-mediated current. Tracazolate increased the current amplitude evoked by a half-maximal concentration (EC(50)) of GABA by 59-fold. The maximum current was increased 23-fold in the presence of a saturating GABA concentration. Concomitant with the increase in the maximum, was a 4-fold decrease in the EC(50). Finally, a mutation in the second transmembrane domain of the delta subunit that increases receptor efficacy (L286S), eliminated the increase in the maximum GABA-activated current. The endogenous neurosteroid, tetrahydrodeoxycorticosterone (THDOC), also decreased the EC(50) and increased the maximum current amplitude, although to a lesser degree than that of tracazolate. Taken all together, these findings indica...Continue Reading

References

Oct 1, 1985·Pharmacology, Biochemistry, and Behavior·J B PatelM E Goldberg
Nov 29, 1986·Brain Research·J N CrawleyS M Paul
Nov 17, 1987·European Journal of Pharmacology·R YoungG Metcalf
Sep 1, 1995·Trends in Pharmacological Sciences·J J LambertJ A Peters
Jan 1, 1994·Annual Review of Neuroscience·R L Macdonald, R W Olsen
Apr 1, 1996·Trends in Neurosciences·R M McKernan, P J Whiting
Oct 27, 1999·Proceedings of the National Academy of Sciences of the United States of America·R M MihalekG E Homanics
Jul 16, 2002·Nature Neuroscience·Inger Sundstrom-PoromaaSheryl S Smith
Jul 18, 2002·Epilepsia·Igor SpigelmanRichard W Olsen
Aug 13, 2002·Current Topics in Medicinal Chemistry·W Sieghart, G Sperk
Mar 12, 2003·Trends in Pharmacological Sciences·Doodipala S Reddy
Nov 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Brandon M StellIstvan Mody
Nov 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·M WallnerR W Olsen
Feb 18, 2004·The Journal of Physiology·Gustav AkkJoe Henry Steinbach
May 18, 2004·The Journal of Physiology·Gustav AkkJoe Henry Steinbach
May 21, 2004·Journal of Neurophysiology·Hua-Jun Feng, Robert L Macdonald
Jun 24, 2004·Molecular Pharmacology·Kendall D W Morris, Jahanshah Amin
Aug 28, 2004·Molecular Pharmacology·Hua-Jun Feng, Robert L Macdonald
Sep 29, 2004·Biochemical Pharmacology·Robert L MacdonaldJingqiong Kang
Dec 23, 2004·Molecular Pharmacology·Patrick S ManganJaideep Kapur
Aug 2, 2005·Epilepsy Currents·Istvan Mody

❮ Previous
Next ❯

Citations

Sep 10, 2013·Progress in Neurobiology·Paula J BruntonJonathan J Hirst
Oct 26, 2011·Proceedings of the National Academy of Sciences of the United States of America·Erwin SigelJürg Gertsch
Jan 15, 2009·The Journal of Biological Chemistry·Kuldeep H KaurErwin Sigel
Oct 6, 2012·The Journal of Biological Chemistry·Erwin Sigel, Michael E Steinmann
Mar 27, 2010·Clinical and Experimental Pharmacology & Physiology·Ming-De WangTorbjörn Bäckström
Oct 16, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Delia BelelliDavid W Cope
Feb 10, 2016·The Journal of Pharmacology and Experimental Therapeutics·Chase Matthew Carver, Doodipala Samba Reddy
Sep 22, 2009·Psychoneuroendocrinology·Nadezhda N ZheleznovaDavid S Weiss
Nov 10, 2013·British Journal of Pharmacology·H-J FengS A Forman
May 15, 2013·The Journal of Pharmacology and Experimental Therapeutics·Xin WuDoodipala Samba Reddy
Sep 14, 2017·Developmental Neurobiology·Joshua M Lorenz-Guertin, Tija C Jacob
Jan 26, 2021·British Journal of Pharmacology·Vivian Wan Yu LiaoPhilip Kiaer Ahring
Jan 3, 2018·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Hua-Jun Feng, Stuart A Forman
May 21, 2011·Biochemical Pharmacology·Anshul Pandya, Jerrel L Yakel
Aug 24, 2021·Journal of Neuroendocrinology·Peter M LambertSteven Mennerick
Sep 18, 2009·Psychoneuroendocrinology·Jeremy J LambertDelia Belelli
Sep 22, 2009·Journal of Neurochemistry·Roland BaurErwin Sigel

❮ 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.