PMID: 12183652Aug 17, 2002Paper

Rapid desensitization of the serotonin(2C) receptor system: effector pathway and agonist dependence

The Journal of Pharmacology and Experimental Therapeutics
Brian D StoutKelly A Berg

Abstract

The serotonin(2C) (5-HT(2C)) receptor couples to multiple effector mechanisms, including phospholipase A(2)-mediated arachidonic acid (AA) release and phospholipase C-mediated production of inositol phosphates (IP). Agonist relative efficacy differs depending upon which response (AA release or IP accumulation) is measured. In this study, we investigated the characteristics and agonist dependence of rapid desensitization of 5-HT(2C) receptor-mediated AA release and IP accumulation measured simultaneously from the same cell population. Pretreatment with 5-HT reduced the ability of a maximal concentration of 5-HT to elicit AA release and IP accumulation by about 60%; however, the AA response desensitized more rapidly (t(1/2) = 1.3 min) than the IP response (t(1/2) = 6.9 min). In addition, desensitization of the IP response was more sensitive (occurred at lower receptor occupancy levels) than the AA response. Moreover, in response to submaximal 5-HT concentrations, after an initial transient desensitization, the AA response was enhanced by up to approximately 250%. After maximal desensitization, both responses recovered, but recovery of the AA response was complete and faster than that for IP. Desensitization of both responses was ...Continue Reading

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Citations

Feb 19, 2005·Psychopharmacology·Aska HayashiKeiji Miyata
Oct 19, 2004·Journal of Affective Disorders·Brian M RossIain Glen
Aug 21, 2003·Progress in Neurobiology·Mark J Millan
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Sep 21, 2020·Reviews in the Neurosciences·Sumaira KhanDivya Vohora
Aug 8, 2018·The International Journal of Neuropsychopharmacology·Kelly A Berg, William P Clarke
Jan 29, 2019·European Journal of Pharmacology·Daniel E FelsingRaymond G Booth

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Cricetus
Phosphatidylinositols
Type C Phospholipases
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Receptors, Tryptamine
Hydroxytryptamine
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Serotonin Agonists

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