Regulation of serotonin 5-HT2C receptors by chronic ligand exposure

European Journal of Pharmacology
Mark G DevlinArthur Christopoulos

Abstract

The effect of ligand pretreatment on human 5-hydroxytryptamine2C (5-HT2C) receptors was examined in CHO cells expressing high (CHO-1C7; 67+/-3 pmol/mg) or low (CHO-1C19; 72+/-10 fmol/mg) levels of the receptor. Seventy-two hours pretreatment of CHO-1C7 cells with various ligands did not affect receptor expression. Pretreatment with inverse agonists enhanced 5-HT-mediated inositol phosphate accumulation with no change in constitutive receptor activity. The enhanced agonist responsiveness was inversely correlated with the intrinsic activity of the pretreatment ligand. Seventy-two hours of pretreatment with the weak agonist, 5-methoxygramine, caused an elevation in constitutive activity but no alteration in 5-HT-mediated signaling. In CHO-1C19 cells, 24 but not 72 h of pretreatment with the inverse agonist mianserin enhanced 5-HT-mediated signaling, with no effect on basal signaling; pretreatment with 5-methoxygramine had no significant effect. These findings highlight differences in the pattern of chronic regulation of 5HT2C receptor signaling between high and low receptor expression levels in a common cellular background.

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Citations

May 13, 2005·Psychopharmacology·S McKieJ F W Deakin
Jun 7, 2005·Journal of Neurochemistry·Tim D WerryArthur Christopoulos
Jan 13, 2006·Trends in Pharmacological Sciences·Richard A Bond, Ad P Ijzerman
Oct 16, 2010·The International Journal of Neuropsychopharmacology·Mark J MillanClotilde Mannoury la Cour
Oct 27, 2016·The Journal of Pharmacology and Experimental Therapeutics·Laura C SullivanWilliam P Clarke
Jan 21, 2020·Neuropharmacology·Philippe De DeurwaerdèreGiuseppe Di Giovanni

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