Suramin is a novel competitive antagonist selective to α1β2γ2 GABAA over ρ1 GABAC receptors

Neuropharmacology
Hui LuoYongchang Chang

Abstract

GABAA and GABAC receptors are both GABA-gated chloride channels with distinct pharmacological properties, mainly in their sensitivity to bicuculline and gabazine. In this study, we found that suramin, a purinergic receptor antagonist, is a novel competitive antagonist selective to GABAA over GABAC receptors. Specifically, suramin antagonized the GABA-induced current and the spontaneous opening current of the wild type α1β2γ2 GABAA receptor with high-level expression in Xenopus oocytes. The antagonism was concentration dependent with an IC50 that varied depending on the concentration of GABA, and with the lowest IC50 of 0.43 μM when antagonizing the spontaneous current. Thus, its potency is slightly higher than bicuculline on the same GABAA receptor. Suramin also antagonized the mouse native brain GABA receptors micro-transplanted into the Xenopus oocytes with its potency depending on the GABA concentration. In addition, in the presence of two fixed concentrations of suramin, the GABA concentration response of the receptor was shifted to the right without reduction of the maximum current. Thus, our results are consistent with that suramin is a competitive antagonist for the α1β2γ2 GABAA receptor. Interestingly, the rank order of...Continue Reading

References

Jan 1, 1994·Annual Review of Neuroscience·R L Macdonald, R W Olsen
Feb 1, 1995·Naunyn-Schmiedeberg's Archives of Pharmacology·K NakazawaK Inoue
Nov 24, 1999·Clinical and Experimental Pharmacology & Physiology·M Chebib, G A Johnston
Jan 19, 2000·Trends in Pharmacological Sciences·J Bormann
Nov 21, 2001·The Journal of Biological Chemistry·Yingcong ZhengDoris F Cully
Sep 19, 2002·Proceedings of the National Academy of Sciences of the United States of America·Ricardo MilediFlavia Trettel
Oct 17, 2002·The Journal of Biological Chemistry·Paul A DaviesEwen F Kirkness
Apr 2, 2003·Fundamental & Clinical Pharmacology·Bernard BouteilleMichel Dumas
Jul 23, 2004·Physiological Reviews·Bernhard BettlerMartin Gassmann
Nov 30, 2004·Clinical and Experimental Pharmacology & Physiology·M Chebib
Dec 8, 2004·The Journal of Biological Chemistry·Igor PutrenkoJoseph A Dent
Aug 30, 2005·European Journal of Pharmacology·Jens D MikkelsenNaheed Mirza
Mar 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ligong ChenJohn E Casida
Aug 30, 2008·Neuropharmacology·Joseph W Lynch
Jan 6, 2009·Annals of the New York Academy of Sciences·Jens D MikkelsenAlexander Kiss
Jan 8, 2009·Physiological Reviews·Edson X AlbuquerqueScott W Rogers
Dec 10, 2009·The Journal of Physiology·Pierre-Jean CorringerCatherine Van Renterghem
Mar 23, 2011·Journal of Autism and Developmental Disorders·Eve G SprattJane M Charles
Jun 27, 2012·The Journal of General Physiology·Snehal Jadey, Anthony Auerbach
Oct 6, 2012·The Journal of Biological Chemistry·Adrian J Wolstenholme
Oct 6, 2012·The Journal of Biological Chemistry·Sarah C R Lummis
Dec 13, 2012·Translational Psychiatry·E LemonnierY Ben-Ari
Mar 13, 2013·The Journal of General Physiology·Prasad Purohit, Anthony Auerbach
Apr 10, 2014·Comprehensive Physiology·Lauren Jacobson
Dec 6, 2014·Frontiers in Cellular Neuroscience·Emily L Casanova, Manuel F Casanova
Dec 18, 2014·Current Medicinal Chemistry·Catia LambertucciRosaria Volpini
Feb 14, 2015·Acta Physiologica·A BarraganB Birnir
Dec 22, 2015·Neuropharmacology·Kenneth A Jacobson, Christa E Müller
Jul 12, 2017·Annals of Clinical and Translational Neurology·Robert K NaviauxJeanne Townsend

❮ Previous
Next ❯

Citations

Dec 18, 2019·Antimicrobial Agents and Chemotherapy·Natalie WiedemarPascal Mäser
Jul 18, 2020·Medicinal Research Reviews·Francesco CalzaferriAntonio G García
Apr 4, 2020·Journal of Agricultural and Food Chemistry·Genyan LiuYoshihisa Ozoe

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

African Trypanosomiasis

African trypanosomiasis, also known as sleeping sickness, is an insect-borne parasitic disease of humans and other animals. It is caused by protozoa of the species Trypanosoma brucei and almost invariably progresses to death unless treated. Discover the latest research on African trypanosomiasis here.

Anthelmintics (ASM)

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.