Serotonin 5-hydroxytryptamine(2A) receptor activation suppresses tumor necrosis factor-alpha-induced inflammation with extraordinary potency.

The Journal of Pharmacology and Experimental Therapeutics
Bangning YuCharles D Nichols

Abstract

The G protein-coupled serotonin 5-hydroxytryptamine (5-HT)(2A) receptor is primarily recognized for its role in brain neurotransmission, where it mediates a wide variety of functions, including certain aspects of cognition. However, there is significant expression of this receptor in peripheral tissues, where its importance is largely unknown. We have now discovered that activation of 5-HT(2A) receptors in primary aortic smooth muscle cells provides a previously unknown and extremely potent inhibition of tumor necrosis factor (TNF)-alpha-mediated inflammation. 5-HT(2A) receptor stimulation with the agonist (R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(R)-DOI] rapidly inhibits a variety of TNF-alpha-mediated proinflammatory markers, including intracellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), and interleukin (IL)-6 gene expression, nitric-oxide synthase activity, and nuclear translocation of nuclear factor kappaB, with IC(50) values of only 10 to 20 pM. It is significant that proinflammatory markers can also be inhibited by (R)-DOI hours after treatment with TNF-alpha. With the exception of a few natural toxins, no current drugs or small molecule therapeutics demonstrate a comparable potency...Continue Reading

References

Aug 31, 1987·Life Sciences·B L Roth, D M Chuang
Feb 3, 1999·Annals of the New York Academy of Sciences·K J Miller, H A Gonzalez
Dec 30, 1999·Journal of Leukocyte Biology·K A Roebuck, A Finnegan
Aug 25, 2000·Mediators of Inflammation·J M HughesC L Armour
Sep 6, 2000·Brain, Behavior, and Immunity·J StefuljK Schauenstein
Jan 26, 2002·Molecular Pharmacology·Karley Y LittleLian Zhang
Dec 20, 2002·The Journal of Pharmacology and Experimental Therapeutics·Deborah M Kurrasch-OrbaughDavid E Nichols
Mar 5, 2003·Free Radical Biology & Medicine·A MarconiP D'Alessio
Oct 17, 2003·Current Drug Targets. Inflammation and Allergy·A M Reimold
Nov 13, 2003·Atherosclerosis·Stefan BlankenbergLaurence Tiret
Feb 6, 2004·Pharmacology & Therapeutics·David E Nichols
Oct 27, 2004·Pharmacology & Therapeutics·Takafumi NagatomoTadazumi Komiyama
May 12, 2005·Neuroscience and Biobehavioral Reviews·Adrian J DunnRenaud de Beaurepaire
Jun 29, 2006·The Journal of Pharmacology and Experimental Therapeutics·Jonathan D UrbanRichard B Mailman
Dec 13, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhong GuoDavid A Geller
Apr 17, 2007·Journal of Affective Disorders·Yong-Ku KimSun-Hwa Park
Jul 14, 2007·Current Opinion in Pharmacology·Richard O WilliamsMarc Feldmann
Sep 8, 2007·BMC Psychiatry·Peter SaetreElena Jazin
Nov 28, 2007·Annual Review of Pathology·Göran K HanssonCecilia Söderberg-Nauclér
Dec 25, 2007·Pharmacology & Therapeutics·Daniel TraceyPaul P Tak
May 15, 2008·Chemical Reviews·David E Nichols, Charles D Nichols

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Citations

Oct 14, 2009·Psychopharmacology·Meredith A FoxDennis L Murphy
Sep 3, 2010·Current Osteoporosis Reports·Itai Bab, Raz Yirmiya
May 23, 2009·Nature Reviews. Immunology·Kevin J Tracey
Jan 6, 2010·Molecular Interventions·Martin Pelletier, Richard M Siegel
Sep 3, 2013·Biological & Pharmaceutical Bulletin·Takuji MachidaMasahiko Hirafuji
Jun 28, 2011·Journal of Pharmacology & Pharmacotherapeutics·Nilesh Chavda Jaykaran
Feb 20, 2015·Hämostaseologie·M MaulerD Duerschmied
Jan 23, 2016·The Journal of Organic Chemistry·Daugirdas T RacysAndrew Sutherland
Feb 5, 2016·Pharmacological Reviews·David E Nichols
Sep 12, 2014·Thrombosis and Haemostasis·Daniel DuerschmiedIngo Ahrens
Aug 2, 2014·Therapeutic Advances in Psychopharmacology·David BaumeisterDerek Tracy
Aug 14, 2018·International Review of Psychiatry·Thomas W Flanagan, Charles D Nichols
Sep 28, 2018·International Review of Psychiatry·Peter S Hendricks
Nov 14, 2018·International Review of Psychiatry·Albert Garcia-Romeu, William A Richards
May 12, 2009·Journal of Thrombosis and Haemostasis : JTH·D DuerschmiedD D Wagner
Jan 15, 2010·Journal of the European Academy of Dermatology and Venereology : JEADV·V LeiboviciE Bachar
Apr 16, 2010·Annals of the New York Academy of Sciences·Itai A Bab, Raz Yirmiya
Jul 16, 2019·Journal of Psychopharmacology·Kim Pc KuypersDavid Nutt
Nov 25, 2014·American Journal of Physiology. Lung Cellular and Molecular Physiology·Felix NauCharles D Nichols
Jan 22, 2020·Protein Science : a Publication of the Protein Society·Chih Hung LoJonathan N Sachs
Jan 5, 2020·Journal of Physiology and Biochemistry·Ondřej VašíčekMilan Číž
May 7, 2020·Regional Anesthesia and Pain Medicine·Joel P CastellanosTimothy Furnish
Dec 27, 2016·Clinical Pharmacology and Therapeutics·D E NicholsC D Nichols
Aug 5, 2017·Frontiers in Cardiovascular Medicine·Nadine HerrDaniel Duerschmied
Feb 16, 2011·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·Pingyuan GongFuchang Zhang
Nov 7, 2017·Chemistry : a European Journal·Stacey WebsterAi-Lan Lee
Sep 9, 2017·Scientific Reports·Jhonny AzuajeEddy Sotelo
Oct 11, 2017·Scientific Reports·Vanja DakicStevens K Rehen
Sep 26, 2020·Frontiers in Immunology·Thomas Wesley HodoAnil Shanker

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