In vivo Schild regression analyses using nonselective 5-HT2C receptor antagonists in a rat operant behavioral assay

Abstract

Taken together, these antagonism profiles suggest that the agonists MK212 and mCPP produce their rate-decreasing effects through a combination of 5-HT receptors with the 5-HT(2C) receptor playing a prominent but not exclusive role.

5-HT2Bserotonin receptor agonist BW723C86 shapes the macrophage gene profile via AhR and impairs monocyte-to-osteoclast differentiation

“…have been widely used in vivo to support the participation of 5-HT 2B in several animal models of disease 73,74,86,87,[89][90][91][124][125][126] , our results suggests the possibility that AhR might have influenced some of these previous results and might have even contributed to the pathological effects of deregulated 5-HT 2B expression or function. As an example, since AhR mediates IL-10 production and promotes immunological tolerance after macrophage capture of apoptotic cells 127 , AhR might contribute to the anti-inflammatory effect of 5-HT 2B in mouse microglia 71 and human monocytes 72 .…”

“…Since human anti-inflammatory M-MØ express 5-HT 7 and 5-HT 2B serotonin receptors 40 and clinically relevant drugs (anesthetics, SSRIs, antimigraine drugs) act via 5-HT 2B 49,51-54 , we sought to determine the consequences of 5-HT 2B engagement in human macrophages using BW723C86, an 5-HT 2B agonist with 10-fold and 100-fold selectivity over human 5-HT 2C and 5-HT 2A , respectively 85 , amply used as in vivo 54,73,74,[86][87][88][89][90][91] and ex vivo 28,66,70 , and with potential therapeutic effects 73,74,91 . Transcriptional profiling of BW723C86-treated M-MØ ( Figure 1A) revealed that the agonist increased the expression of 357 annotated genes and downregulated the expression of 398 genes (adj p<0.002) ( Figure 1B, Supplementary Tables II and III).…”

“…To identify genes whose expression is regulated by BW723C86 in a 5-HT 2B -dependent manner, the transcriptional effects of the 5-HT 2B agonist were also determined in the presence of SB204741 (BW723C86 + SB204741) ( Figure 1A, Supplementary Table IV), a selective 5-HT 2B antagonist with 100-fold selectivity over 5-HT 2C and 5-HT 2A 85 that is widely used in vivo 9,61,63,90,96 . We reasoned that the genes significantly modulated by BW723C86, but not by BW723C86+SB204741, would represent bona fide 5-HT 2B -regulated genes.…”

Endogenous 5-HT2C Receptors Phosphorylate the cAMP Response Element Binding Protein via Protein Kinase C-Promoted Activation of Extracellular-Regulated Kinases-1/2 in Hypothalamic mHypoA-2/10 Cells

“…(C) ERK-1/2 phosphorylation in mHypoA-2/10 cells was measured by whole-cell ELISA after stimulation with increasing concentration of 5-HT or WAY-161,503 for 3 minutes. Data of four experiments performed in quadruplicate were interacts with other CRE-activating 5-HTRs besides HT 2C R. To further evaluate the role of distinct 5-HTR in hypothalamic CRE activation, we took advantage of the 5-HT 2C R antagonists SB-242,084 or RS-102,221, the 5-HT 2A R antagonist EMD-281,014, and the 5-HT 2B R antagonist RS-127,455 (Cussac et al, 2000;Walker et al, 2007). Both 5-HT 2C R, but none of the other antagonists, blunted WAY-161,503-induced CRE-dependent gene expression (Fig.…”

Serotonin (5-HT) Shapes the Macrophage Gene Profile through the 5-HT2B–Dependent Activation of the Aryl Hydrocarbon Receptor

“…agonist with 10-fold and 100-fold selectivity over human 5-HT2C and 5-HT2A, respectively 86 , amply used as in vivo 54,73,74,[87][88][89][90][91][92] and ex vivo 28,66,70 , and with potential therapeutic effects 73,74,92 .…”