Niswender CM, Sanders-Bush E, Emeson RB.
Identification and characterization of RNA editing events within the 5-HT2C receptor.
Ann N Y Acad Sci 1998 Dec 15;861:38-48
"Editing events at four major positions, termed A, B, C and D, as well as one minor site termed C', are predicted to alter amino acids within the second intracellular loop of the G-protein coupled 5-HT2C receptor. Editing is mediated by at least two members of a family of adenosine deaminases and is contingent upon the presence of an extensive RNA duplex structure formed by exonic and intronic sequences of 5-HT2C receptor precursor messenger RNA (pre-mRNA)." [Abstract]
Price, Raymond D., Sanders-Bush, Elaine
RNA Editing of the Human Serotonin 5-HT2C Receptor Delays Agonist-Stimulated Calcium Release
Mol Pharmacol 2000 58: 859-862
"The hVGV isoform shows a different pattern of calcium release compared with the hINI and hVSV isoforms, with a smaller peak height and longer latency." [Full Text]
Niswender CM, Herrick-Davis K, Dilley GE, Meltzer HY, Overholser JC, Stockmeier CA, Emeson RB, Sanders-Bush E.
RNA editing of the human serotonin 5-HT2C receptor. alterations in suicide and implications for serotonergic pharmacotherapy
Neuropsychopharmacology 2001 May;24(5):478-91 .
"An examination of the efficiencies of RNA editing of the 5-HT(2C)R in prefrontal cortex of control individuals vs. subjects diagnosed with schizophrenia or major depressive disorder revealed no significant differences in RNA editing among the three populations. However, subjects who had committed suicide (regardless of diagnosis) exhibited a statistically significant elevation of editing at the A-site, which is predicted to change the amino acid sequence in the second intracellular loop of the 5-HT(2C)R. These findings suggest that alterations in RNA editing may contribute to or complicate therapy in certain psychiatric disorders." [Abstract]
Bonaccorso S, Meltzer H, Li Z, Dai J, Alboszta A, Ichikawa J.
SR46349-B, a 5-HT(2A/2C) Receptor Antagonist, Potentiates Haloperidol-induced Dopamine Release in Rat Medial Prefrontal Cortex and Nucleus Accumbens.
Neuropsychopharmacology 2002 Sep;27(3):430
"The combination of M100907, a putative antipsychotic drug (APD) and serotonin (5-HT)(2A) antagonist, and the typical APD haloperidol, can enhance dopamine (DA) release in rat medial prefrontal cortex (mPFC), an effect which has been postulated to be of value to improve cognition and negative symptoms. The present study demonstrated that another putative APD and 5-HT(2A/2C) antagonist, SR46349-B (10 mg/kg, but not 1-3 mg/kg) alone, but not M100907 (0.1 and 3 mg/kg) alone, increased mPFC DA release, whereas neither drug alone affected nucleus accumbens (NAC) DA release. Neither SR46349-B nor M100907 alone affected nucleus accumbens (NAC) DA release. Neither SR46349-B nor M100907 alone affected nucleus accumbens (NAC) DA release. SR46349-B (3 mg/kg) potentiated haloperidol-induced DA release in both regions, whereas M100907 (0.1 mg/kg) potentiated haloperidol (0.1 mg/kg)-induced mPFC DA release and inhibited it in the NAC." [Abstract]
Stout, Brian D., Clarke, William P., Berg, Kelly A.
Rapid Desensitization of the Serotonin2C Receptor System: Effector Pathway and Agonist Dependence
J Pharmacol Exp Ther 2002 302: 957-962
"The serotonin2C (5-HT2C) receptor couples to multiple effector mechanisms, including phospholipase A2-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-HT2C 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 (t1/2 = 1.3 min) than the IP response (t1/2 = 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 ~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 also agonist-dependent, and the capacity of agonists to elicit desensitization was not related to their efficacy to activate signaling. These data suggest that desensitization of the 5-HT2C receptor system is both agonist- and effector pathway-dependent and underscore the need to study multiple cellular responses to multiple agonists to understand receptor-mediated signaling systems." [Abstract]
Chen CX, Cho DS, Wang Q, Lai F, Carter KC, Nishikura K.
A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both single- and double-stranded RNA binding domains.
RNA 2000 May;6(5):755-67
"The presence of this ssRNA-binding domain as well as its expression in restricted brain regions and postmitotic neurons make ADAR3 distinct from the other two ADAR gene family members, editing competent ADAR1 and ADAR2. ADAR3 inhibited in vitro the activities of RNA editing enzymes of the ADAR gene family, raising the possibility of a regulatory role in RNA editing." [Abstract]
Becamel, Carine, Alonso, Gerard, Galeotti, Nathalie, Demey, Emmanuelle, Jouin, Patrick, Ullmer, Christoph, Dumuis, Aline, Bockaert, Joel, Marin, Philippe
Synaptic multiprotein complexes associated with 5-HT2C receptors: a proteomic approach
EMBO J. 2002 21: 2332-2342 [Abstract]
Wang, Qingde, O'Brien, Peter J., Chen, Chun-Xia, Cho, Dan-Sung C., Murray, John M., Nishikura, Kazuko
Altered G Protein-Coupling Functions of RNA Editing Isoform and Splicing Variant Serotonin2C Receptors
J Neurochem 2000 74: 1290-1300
"Asp158 present in the IDV isoform may mimic a structure similar to phosphorylated Ser158, providing a possible mechanism for fine adjustment of the constitutive activity via RNA editing and consequent phosphorylation of the edited Ser158 by a casein kinase II-like activity." [Abstract]
Burns CM, Chu H, Rueter SM, Hutchinson LK, Canton H, Sanders-Bush E, Emeson RB.
Regulation of serotonin-2C receptor G-protein coupling by RNA editing.
Nature 1997 May 15;387(6630):303-8 [Abstract]
Carine Bécamel, Andrea Figge, Sebastian Poliak, Aline Dumuis, Elior Peles, Joël Bockaert, Hermann Lübbert, and Christoph Ullmer
Interaction of Serotonin 5-Hydroxytryptamine Type 2C Receptors with PDZ10 of the Multi-PDZ Domain Protein MUPP1
J. Biol. Chem. 276: 12974-12982, April 20, 2001. [Full Text]
Jon R. Backstrom, Raymond D. Price, Darcie T. Reasoner, and Elaine Sanders-Bush
Deletion of the Serotonin 5-HT2C Receptor PDZ Recognition Motif Prevents Receptor Phosphorylation and Delays Resensitization of Receptor Responses
J. Biol. Chem. 275: 23620-23626, August 4, 2000. [Full Text]
Li Q, Wichems CH, Ma L, Van de Kar LD, Garcia F, Murphy DL.
Brain region-specific alterations of 5-HT2A and 5-HT2C receptors in serotonin transporter knockout mice.
J Neurochem 2003 Mar;84(6):1256-65
"The aim of the present studies was to determine the effects of reduced or absent serotonin (5-HT) transporters (5-HTTs) on 5-HT2A and 5-HT2C receptors. The density of 5-HT2C receptors was significantly increased in the amygdala and choroid plexus of 5-HTT knockout mice. On the other hand, the density of 5-HT2A receptors was significantly increased in the hypothalamus and septum, but reduced in the striatum, of 5-HTT knockout mice. However, 5-HT2A mRNA was not changed in any brain region measured. 5-HT2C mRNA was significantly reduced in the choroid plexus and lateral habenula nucleus of these mice. The function of 5-HT2A receptors was evaluated by hormonal responses to (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Oxytocin, but not adrenocorticotrophic hormone or corticosterone, responses to DOI were significantly greater in 5-HTT knockout mice. In addition, Gq and G11 proteins were not significantly changed in any brain region measured. The present results suggest that the constitutive alteration in the function of 5-HTTs changes the density of 5-HT2A and 5-HT2C receptors in a brain region-specific manner. These changes may not be mediated by alterations in their gene expression or in the level of Gq/11 proteins. The alterations in these receptors may be related to the altered behaviors of 5-HTT knockout mice." [Abstract]
Kuhn KU, Quednow BB, Bagli M, Meyer K, Feuchtl A, Westheide J, Frahnert C, Maier W, Rao ML.
Allelic Variants of the Serotonin2C Receptor and Neuroendocrinological Responses to the Serotonin2C Receptor Agonist m-Chlorophenylpiperazine in Healthy Male Volunteers.
Pharmacopsychiatry 2002 Nov;35(6):226-30
"The neurotransmitter serotonin (5-HT) possesses several receptors and their subtypes, some of which are polymorphic, such as the 5-HT 2C receptor. The latter has been implicated in the control of neuroendocrine function, and has been discussed in the pathophysiology and pharmacotherapy of psychiatric disorders such as obsessive-compulsive disorder, panic disorder and bipolar affective disorder. To investigate whether the 5-HT 2C receptor polymorphism contributes to the variation of neuroendocrinological responses elicited by activation of the hypothalamic-pituitary axis, we performed an m-chlorophenylpiperazine (m-CPP) challenge and monitored m-CPP and ACTH, cortisol and prolactin plasma levels in 16 healthy male volunteers carrying the common 5-HT 2C -cys-23 receptor gene and 16 healthy male volunteers carrying the less frequent 5-HT 2C -ser-23 receptor gene. The 5-HT 2C polymorphism contributed little to the variation of the scores regarding hormonal responses of ACTH, cortisol and prolactin to the m-CPP challenge. The group carrying the rare 5-HT 2C -ser-23 receptor gene showed a faster and stronger but not statistically significant ACTH response to the challenge. However, it is noteworthy that there is a 'medium' effect size of the ACTH response according to the conventions of Cohen, and thus comparable to other studies. Both groups show similar major scores in the Temperament and Character Inventory (TCI)." [Abstract]
Lerer B, Macciardi F, Segman RH, Adolfsson R, Blackwood D, Blairy S, Del Favero J, Dikeos DG, Kaneva R, Lilli R, Massat I, Milanova V, Muir W, Noethen M, Oruc L, Petrova T, Papadimitriou GN, Rietschel M, Serretti A, Souery D, Van Gestel S, Van Broeckhoven C, Mendlewicz J.
Variability of 5-HT2C receptor cys23ser polymorphism among European populations and vulnerability to affective disorder.
Mol Psychiatry 2001 Sep;6(5):579-85 [Full Text]
Lucas, Guillaume, Spampinato, Umberto
Role of Striatal Serotonin2A and Serotonin2C Receptor Subtypes in the Control of In Vivo Dopamine Outflow in the Rat Striatum
J Neurochem 2000 74: 693-701
"These results indicate that striatal 5-HT2A receptors, probably through activation of DA synthesis, positively modulate DA outflow only under activated conditions. In contrast, striatal 5-HT2C receptors exert a facilitatory control on basal DA efflux, which appears to be both tonic and phasic." [Abstract]
Virkkunen M, Goldman D, Linnoila M.
Serotonin in alcoholic violent offenders.
Ciba Found Symp 1996;194:168-77; discussion 177-82
"Thus far, polymorphisms of the tryptophan hydroxylase (TPH) and 5-HT2C receptor genes have been the most informative findings." [Abstract]
Evans J, Reeves B, Platt H, Leibenau A, Goldman D, Jefferson K, Nutt D.
Impulsiveness, serotonin genes and repetition of deliberate self-harm (DSH).
Psychol Med 2000 Nov;30(6):1327-34
"Males with the 5-HT2c serine variant were more impulsive than those with the cysteine variant (039 standardized units, P = 0.041, 95% CI 0.017 to 0.076)." [Abstract]
Canton, H, Emeson, RB, Barker, EL, Backstrom, JR, Lu, JT, Chang, MS, Sanders-Bush, E
Identification, molecular cloning, and distribution of a short variant of the 5-hydroxytryptamine2C receptor produced by alternative splicing
Mol Pharmacol 1996 50: 799-807 [Abstract]
Fitzgerald LW, Iyer G, Conklin DS, Krause CM, Marshall A, Patterson JP, Tran DP, Jonak GJ, Hartig PR.
Messenger RNA editing of the human serotonin 5-HT2C receptor.
Neuropsychopharmacology 1999 Aug;21(2 Suppl):82S-90S
"We observed that editing reduces both the binding affinity and functional potency of agonists for recombinant human 5-HT2C receptor isoforms. This effect on binding affinity was proportional to the agonist's intrinsic activity, with full agonists most affected, and antagonists showing no effect." [Abstract]
Berg, KA, Maayani, S, Clarke, WP
5-hydroxytryptamine2C receptor activation inhibits 5- hydroxytryptamine1B-like receptor function via arachidonic acid metabolism
Mol Pharmacol 1996 50: 1017-1023
"5-hydroxytryptamine2C receptor activation inhibits 5- hydroxytryptamine1B-like receptor function via arachidonic acid metabolism." [Abstract]
Herrick-Davis, Katharine, Grinde, Ellinor, Niswender, Colleen M.
Serotonin 5-HT2C Receptor RNA Editing Alters Receptor Basal Activity: Implications for Serotonergic Signal Transduction
J Neurochem 1999 73: 1711-1717 [Abstract]
Berg, Kelly A., Cropper, Jodie D., Niswender, Colleen M., Sanders-Bush, Elaine, Emeson, Ronald B., Clarke, William P.
RNA-editing of the 5-HT2C receptor alters agonist-receptor-effector coupling specificity
Br. J. Pharmacol. 2001 134: 386-392 [Abstract]
Berg, Kelly A., Maayani, Saul, Goldfarb, Joseph, Scaramellini, Clare, Leff, Paul, Clarke, William P.
Effector Pathway-Dependent Relative Efficacy at Serotonin Type 2A and 2C Receptors: Evidence for Agonist-Directed Trafficking of Receptor Stimulus
Mol Pharmacol 1998 54: 94-104 [Full Text]
LAPPALAINEN, J;ZHANG, L;DEAN, M;OZ, M;OZAKI, N;YU, DH;VIRKKUNEN, M;WEIGHT, F;LINNOILA, M;GOLDMAN, D
IDENTIFICATION, EXPRESSION, AND PHARMACOLOGY OF A CYS(23)-SER(23) SUBSTITUTION IN THE HUMAN 5-HT2C RECEPTOR GENE (HTR2C)
GENOMICS 27: (2) 274-279 MAY 20 1995
"Allele frequencies in unrelated Caucasians were 0.13 and 0.87 for 5-HT2Cser and 5-HT2Ccys, respectively." [Abstract]
Di Matteo V, Di Giovanni G, Di Mascio M, Esposito E.
SB 242084, a selective serotonin2C receptor antagonist, increases dopaminergic transmission in the mesolimbic system.
Neuropharmacology 1999 Aug;38(8):1195-205 [Abstract]
Pompeiano M, Palacios JM, Mengod G.
Distribution of the serotonin 5-HT2 receptor family mRNAs: comparison between 5-HT2A and 5-HT2C receptors.
Brain Res Mol Brain Res 1994 Apr;23(1-2):163-78 [Abstract]
De Deurwaerdere, Philippe, Chesselet, Marie-Francoise
Nigrostriatal Lesions Alter Oral Dyskinesia and c-Fos Expression Induced by the Serotonin Agonist 1-(m-Chlorophenyl)piperazine in Adult Rats
J. Neurosci. 2000 20: 5170-5178 [Full Text]
The role of serotonin in antipsychotic drug action.
Neuropsychopharmacology 1999 Aug;21(2 Suppl):106S-115S
"Stimulation of the 5-HT1a receptor appears to produce many of the same effects as antagonism of the 5-HT2a receptor while antagonism of the 5-HT2c receptor appears to diminish some of the actions of 5-HT2a receptor antagonism." [Abstract]
Segman RH, Ebstein RP, Heresco-Levy U, Gorfine M, Avnon M, Gur E, Nemanov L, Lerer B.
Schizophrenia, chronic hospitalization and the 5-HT2C receptor gene.
Psychiatr Genet 1997 Summer;7(2):75-8
"However, proportion of time spent in hospital since the first admission was significantly greater in patients hemi- of homozygous for the 5-HT2Cser allele than in patients carrying other genotypes (p = 0.006). The 5-HT2Cser genotype conferred a 3.3-fold increased risk for lifetime hospitalization exceeding 10 years. Genetically determined variation in the 5-HT2C receptor may influence the clinical course and phenotypic expression of schizophrenia." [Abstract]
Roger M. Nitsch, Meihua Deng, John H. Growdon, and Richard J. Wurtman
Serotonin 5-HT2a and 5-HT2c Receptors Stimulate Amyloid Precursor Protein Ectodomain Secretion
J. Biol. Chem. 271: 4188-4194, February 23, 1996. [Full Text]
Cowen PJ, Clifford EM, Walsh AE, Williams C, Fairburn CG.
Moderate dieting causes 5-HT2C receptor supersensitivity.
Psychol Med 1996 Nov;26(6):1155-9 [Abstract]
HEISLER, L. K., CHU, H.-M, TECOTT, L. H.
Epilepsy and Obesity in Serotonin 5-HT2C Receptor Mutant Mice
Ann NY Acad Sci 1998 861: 74-78 [Abstract]
Benjamin J, Ebstein RP, Belmaker RH.
Isr J Psychiatry Relat Sci 1997;34(4):270-80
"In the Israeli sample we also found an interaction between the D4DR gene and the serotonin 2C receptor gene (5-HT2C) with a marked effect on the trait of reward dependence." [Abstract]
Segman RH, Heresco-Levy U, Finkel B, Inbar R, Neeman T, Schlafman M, Dorevitch A, Yakir A, Lerner A, Goltser T, Shelevoy A, Lerer B.
Association between the serotonin 2C receptor gene and tardive dyskinesia in chronic schizophrenia: additive contribution of 5-HT2Cser and DRD3gly alleles to susceptibility.
Psychopharmacology (Berl) 2000 Nov;152(4):408-13
"We found a significant excess of 5-HT2Cser alleles in schizophrenia patients with TD (27.2%) compared to patients without TD (14.6%) and normal controls (14.2%; chi2=6.4, df 2, P=0.03) which was due to the female patients (chi2=8.6, df 2, P=0.01). Among the female TD patients there was an excess of cys-ser and ser-ser genotypes (chi2= 11.9, df 4, P=0.02)."
Gurevich I, Tamir H, Arango V, Dwork AJ, Mann JJ, Schmauss C.
Altered editing of serotonin 2C receptor pre-mRNA in the prefrontal cortex of depressed suicide victims.
Neuron. 2002 Apr 25;34(3):327-8.
"Five adenosines within the coding sequence of the serotonin 2C receptor (5-HT2C) pre-mRNA are converted to inosines by RNA editing (named A, B, C' (E), C, and D sites). In human prefrontal cortex (PFC), the most abundant 5-HT2C mRNA sequences result from editing at the A site, or from the editing combinations AC'C, ABCD, and ABD. In suicide victims with a history of major depression, C' site editing is significantly increased, D site editing is significantly decreased, and the C site shows a trend toward increased editing. Treatment of mice with the antidepressant drug fluoxetine (Prozac) causes changes in C', C, and D site editing that are exactly opposite to those seen in suicide victims. Thus, one outcome of fluoxetine treatment may be to reverse the abnormalities in 5-HT2C pre-mRNA editing seen in depressed suicide victims." [Abstract] [PDF]
Gurevich I, Englander MT, Adlersberg M, Siegal NB, Schmauss C.
Modulation of serotonin 2C receptor editing by sustained changes in serotonergic neurotransmission.
J Neurosci 2002 Dec 15;22(24):10529-32
"Serotonin 2C (5-HT2C) receptor pre-mRNA is a substrate for RNA editing enzymes that convert five adenosines (named A, B, C', C, and D editing sites) to inosines. Editing of two of these sites (C' and C) is crucial for decreasing the efficiency of the receptor to activate G-protein. Nucleotide sequence analysis of mouse forebrain neocortical 5-HT2C mRNA isoforms revealed that editing at these two sites is regulated in a serotonin-dependent manner. In serotonin-depleted mice, C'- and C-site editing is significantly decreased. This results in an increased expression of 5-HT2C mRNA isoforms encoding receptors with higher sensitivity to serotonin. In contrast, a 4 d treatment with the 5-HT2A/2C agonist (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane significantly increases the editing frequency at the C' site and leads to increased expression of 5-HT2C mRNA isoforms encoding receptors that activate G-protein least efficiently. None of the drug treatments led to alterations in cytoplasmic 5-HT2C mRNA levels. These data indicate that editing of 5-HT2C pre-mRNA is a mechanism that retains basic response properties of 5-HT2C receptors in the face of changing synaptic input to keep receptor activation within an optimal range for information processing." [Abstract] [PDF]
Iwamoto K, Kato T.
RNA editing of serotonin 2C receptor in human postmortem brains of major mental disorders.
Neurosci Lett. 2003 Aug 7;346(3):169-72.
"The importance of serotonin 2C receptor (HTR2C) in mental disorders has been implicated by studies of HTR2C-deficient mice and linkage and association studies. Recent studies have revealed that RNA editing of HTR2C is involved in mental disorders. Here we examined RNA editing efficiencies of site A and D of HTR2C in the prefrontal cortex samples of patients with bipolar disorder, schizophrenia, and major depression as well as control subjects by using primer extension combined with denaturing high performance liquid chromatography. Postmortem samples were donated by the Stanley Foundation Brain Collection. We could not find significant alterations of RNA editing efficiencies of these sites in patients. However, we found trends for increased RNA editing efficiencies of site D in depressive patients (P=0.08) and site A in suicide victims (P=0.07). These findings are in accordance with the previous findings, and suggest that altered RNA editing of HTR2C may have some significance in major depression and suicide." [Abstract]
More RNA editing information is listed here.
Blackburn TP, Minabe Y, Middlemiss DN, Shirayama Y, Hashimoto K, Ashby CR Jr.
Effect of acute and chronic administration of the selective 5-HT2C receptor antagonist SB-243213 on midbrain dopamine neurons in the rat: An in vivo extracellular single cell study.
Synapse 2002 Dec 1;46(3):129-139
"Overall, our results indicate that antagonism of the 5-HT(2C) receptor alters the activity of midbrain DA neurons in anesthetized rats and suggest that SB-243213 has an atypical antipsychotic profile following chronic administration." [Abstract]
Becamel, Carine, Alonso, Gerard, Galeotti, Nathalie, Demey, Emmanuelle, Jouin, Patrick, Ullmer, Christoph, Dumuis, Aline, Bockaert, Joel, Marin, Philippe
Synaptic multiprotein complexes associated with 5-HT2C receptors: a proteomic approach
EMBO J. 2002 21: 2332-2342
"Using a proteomic approach based on peptide affinity chromatography followed by mass spectrometry and immunoblotting, we have identified 15 proteins that interact with the C- terminal tail of the 5-hydroxytryptamine 2C (5-HT2C) receptor, a GPCR. These proteins include several synaptic multidomain proteins containing one or several PDZ domains (PSD95 and the proteins of the tripartite complex Veli3CASKMint1), proteins of the actin/spectrin cytoskeleton and signalling proteins. Coimmunoprecipitation experiments showed that 5-HT2C receptors interact with PSD95 and the Veli3CASKMint1 complex in vivo. Electron microscopy also indicated a synaptic enrichment of Veli3 and 5-HT2C receptors and their colocalization in microvilli of choroidal cells. These results indicate that the 5-HT2C receptor is associated with protein networks that are important for its synaptic localization and its coupling to the signalling machinery." [Abstract]
Yong Liu, Ronald B. Emeson, and Charles E. Samuel
Serotonin-2C Receptor Pre-mRNA Editing in Rat Brain and in Vitro by Splice Site Variants of the Interferon-inducible Double-stranded RNA-specific Adenosine Deaminase ADAR1
J. Biol. Chem. 274: 18351-18358, 1999. [Full Text]
Mike Chang, Lianshan Zhang, James P. Tam, and Elaine Sanders-Bush
Dissecting G Protein-coupled Receptor Signaling Pathways with Membrane-permeable Blocking Peptides. ENDOGENOUS 5-HT2C RECEPTORS IN CHOROID PLEXUS EPITHELIAL CELLS
J. Biol. Chem. 275: 7021-7029, March 10, 2000. [Full Text]
Cussac, Didier, Newman-Tancredi, Adrian, Duqueyroix, Delphine, Pasteau, Valerie, Millan, Mark J.
Differential Activation of Gq/11 and Gi3 Proteins at 5-Hydroxytryptamine2C Receptors Revealed by Antibody Capture Assays: Influence of Receptor Reserve and Relationship to Agonist-Directed Trafficking
Mol Pharmacol 2002 62: 578-589 [Abstract]
Berg, Kelly A., Stout, Brian D., Cropper, Jodie D., Maayani, Saul, Clarke, William P.
Novel Actions of Inverse Agonists on 5-HT2C Receptor Systems
Mol Pharmacol 1999 55: 863-872 [Full Text]
Sallese, Michele, Mariggio, Stefania, D'Urbano, Etrusca, Iacovelli, Luisa, De Blasi, Antonio
Selective Regulation of Gq Signaling by G Protein-Coupled Receptor Kinase 2: Direct Interaction of Kinase N Terminus with Activated Galpha q
Mol Pharmacol 2000 57: 826-831 [Full Text]
Hurley, Joyce H., Bloem, Laura J., Pavalko, Fred, Liu, Jian, Tian, Mingting, Simon, Jay R., Yu, Lei
Structure--Function Studies of the Eighth Hydrophobic Domain of a Serotonin Receptor
J Neurochem 1999 72: 413-421 [Abstract]
Raymond D. Price, David M. Weiner, Mike S. S. Chang, and Elaine Sanders-Bush
RNA Editing of the Human Serotonin 5-HT2C Receptor Alters Receptor-mediated Activation of G13 Protein
J. Biol. Chem. 276: 44663-44668, November 30, 2001.
"Taken together, these data support the hypothesis that the INI isoform has the ability to activate Gq, G13, and G15, whereas the edited VSV and VGV receptor isoforms can efficiently activate only the Gq family of G-proteins." [Full Text]
Di Giovanni G, De Deurwaerdere P, Di Mascio M, Di Matteo V, Esposito E, Spampinato U.
Selective blockade of serotonin-2C/2B receptors enhances mesolimbic and mesostriatal dopaminergic function: a combined in vivo electrophysiological and microdialysis study.
Neuroscience 1999;91(2):587-97 [Abstract]
Heisler LK, Tecott LH.
A paradoxical locomotor response in serotonin 5-HT(2C) receptor mutant mice.
J Neurosci 2000 Apr 15;20(8):RC71
"We report that a single receptor gene mutation produces a paradoxical response to the nonspecific serotonin receptor agonist m-chlorophenylpiperazine (mCPP). Although this compound normally suppresses locomotion, it produces hyperactivity in mice bearing a targeted mutation of the 5-HT(2C) receptor gene. This effect was blocked by pretreatment with a 5-HT(1B) receptor antagonist, indicating that the behavioral consequences of mCPP-induced 5-HT(1B) receptor stimulation are unmasked in animals devoid of 5-HT(2C) receptor function." [Abstract]
Westphal, RS, Backstrom, JR, Sanders-Bush, E
Increased basal phosphorylation of the constitutively active serotonin 2C receptor accompanies agonist-mediated desensitization
Mol Pharmacol 1995 48: 200-205 [Abstract]
Westphal, RS, Sanders-Bush, E
Differences in agonist-independent and -dependent 5-hydroxytryptamine2C receptor-mediated cell division
Mol Pharmacol 1996 49: 474-480 [Abstract]
Laurence H. Tecott, Sheree F. Logue, Jeanne M. Wehner, and Julie A. Kauer
Perturbed dentate gyrus function in serotonin 5-HT2C receptor mutant mice
PNAS 95: 15026-15031, December 8, 1998. [Full Text]
Grottick, Andrew J., Fletcher, Paul J., Higgins, Guy A.
Studies to Investigate the Role of 5-HT2C Receptors on Cocaine- and Food-Maintained Behavior
J Pharmacol Exp Ther 2000 295: 1183-1191
"Taken together, these studies suggest that, in addition to reducing food intake, 5-HT2C receptor agonists reduce cocaine-reinforced behavior. This would be consistent with electrophysiological and biochemical evidence suggesting an important modulatory influence of 5-HT2C receptor activation on mesolimbic dopamine function." [Full Text]
McMahonLance R, LR McMahon, M Filip, KA Cunningham
Differential regulation of the mesoaccumbens circuit by serotonin 5-hydroxytryptamine (5-ht)2a and 5-ht2c receptors
JOURNAL OF NEUROSCIENCE: THE OFFICIAL JOURNAL OF THE SOCIETY FOR NEUROSCIENCE, THE , 21(19):7781-7787 2001
"These findings are the first to demonstrate that the behavioral effects of cocaine are generated in part by activation of 5-HT(2A)Rs in the VTA and by activation of 5-HT(2C)Rs in the NAc shell." [Abstract]
Herrick-Davis, Katharine, Grinde, Ellinor, Teitler, Milt
Inverse Agonist Activity of Atypical Antipsychotic Drugs at Human 5-Hydroxytryptamine2C Receptors
J Pharmacol Exp Ther 2000 295: 226-232 [Full Text]
-note that 5-HT2C agonism as an atypical antipsychotic mechanism of efficacy is purely conjectural
Berg, Kelly A., Stout, Brian D., Maayani, Saul, Clarke, William P.
Differences in Rapid Desensitization of 5-Hydroxytryptamine2A and 5-Hydroxytryptamine2C Receptor-Mediated Phospholipase C Activation
J Pharmacol Exp Ther 2001 299: 593-602 [Abstract]
Deurwaerdere, Philippe De, Spampinato, Umberto
Role of Serotonin2A and Serotonin2B/2C Receptor Subtypes in the Control of Accumbal and Striatal Dopamine Release Elicited In Vivo by Dorsal Raphe Nucleus Electrical Stimulation
J Neurochem 1999 73: 1033-1042 [Abstract]
Maura, Guido, Marcoli, Manuela, Pepicelli, Olimpia, Rosu, Christian, Viola, Concetta, Raiteri, Maurizio
Serotonin inhibition of the NMDA receptor/nitric oxide/cyclic GMP pathway in human neocortex slices: involvement of 5-HT2C and 5-HT1A receptors
Br. J. Pharmacol. 2000 130: 1853-1858 [Abstract]
VERBEKE, MARLEEN, VAN DE VOORDE, JOHAN, DE RIDDER, LEO, LAMEIRE, NORBERT
Beneficial Effect of Serotonin 5-HT2-Receptor Antagonism on Renal Blood Flow Autoregulation in Cyclosporin-Treated Rats
J Am Soc Nephrol 1999 10: 28-34 [Full Text]
Feng, Jian, Cai, Xiang, Zhao, Jinghui, Yan, Zhen
Serotonin Receptors Modulate GABAA Receptor Channels through Activation of Anchored Protein Kinase C in Prefrontal Cortical Neurons
J. Neurosci. 2001 21: 6502-6511
"Our single-cell mRNA profiling experiments have shown that 5-HT2A receptors are expressed in the majority of PFC pyramidal neurons (>80%), whereas 5-HT2C receptors are detected in only one-third of these cells, suggesting that the effects of DOI on GABAA currents found in most PFC pyramidal neurons can be primarily attributed to 5-HT2A receptors." [Full Text]
GABAB Receptors, Monoamine Receptors, and Postsynaptic Inositol Trisphosphate-Induced Ca2+ Release Are Involved in the Induction of Long-Term Potentiation at Visual Cortical Inhibitory Synapses
J. Neurosci. 1996 16: 6342-6352
"Inhibitory responses of layer V cells evoked by layer IV stimulation were studied in developing rat visual cortex slices by using intracellular and whole-cell recording methods. LTP induction was prevented by the application of an antagonist for GABAB receptors but not for GABAA or metabotropic glutamate receptors. Inhibition of postsynaptic G-proteins, phospholipase C, inositol trisphosphate (IP3) receptors, or Ca2+ increase prevented the generation of LTP, as did the blockade of GABAB receptors." [Full text]
Reynolds GP, Zhang ZJ, Zhang XB.
Association of antipsychotic drug-induced weight gain with a 5-HT2C receptor gene polymorphism.
Lancet 2002 Jun 15;359(9323):2086-7
"We noted significantly less weight gain in patients with the -759T variant allele (p=0.0003) than in those without this allele, who were more likely to have substantial (>7%) weight gain (p=0.002). We have identified a genetic factor that is associated with antipsychotic drug-induced weight gain." [Abstract]
Lindberg N, Virkkunen M, Tani P, Appelberg B, Virkkala J, Rimon R, Porkka-Heiskanen T.
Effect of a single-dose of olanzapine on sleep in healthy females and males.
Int Clin Psychopharmacol 2002 Jul;17(4):177-84
"The difference between the sexes could not be explained by differences in body mass index. Olanzapine affects sleep probably through 5-HT2C receptors. The receptor gene is located on the X-chromosome, inducing an allelic difference between the females and males. This difference may contribute to the different effects of olanzapine on sleep." [Abstract]
Arjona A, Pooler A, Lee R, Wurtman R.
Effect of a 5-HT(2C) serotonin agonist, dexnorfenfluramine, on amyloid precursor protein metabolism in guinea pigs.
Brain Res 2002 Sep 27;951(1):135
"These data indicate that the pharmacological activation of 5-HT(2C) receptors can stimulate CSF APP(s) secretion and reduce Abeta production in vivo. Hence 5-HT(2C) receptors, which apparently are localized to the brain, may represent useful targets for the development of treatments for Alzheimer's disease." [Abstract]
Millan MJ, Girardon S, Dekeyne A.
5-HT2C receptors are involved in the discriminative stimulus effects of citalopram in rats.
Psychopharmacology (Berl) 1999 Mar;142(4):432-4
"The preferential, high efficacy agonist at 5-HT2C receptors, Ro60-0175, dose-dependently generalized to citalopram with an ED50 of 0.3 mg/kg, IP. Further, the selective 5-HT2C receptor antagonist, SB242,084, dose-dependently (ED50=0.1 mg/kg, IP) blocked the citalopram DS. These data suggest that 5-HT2C receptors are involved in the DS properties of the SSRI, citalopram, in rats. They do not, however, exclude a potential role of other 5-HT receptor types." [Abstract]
Palvimaki EP, Roth BL, Majasuo H, Laakso A, Kuoppamaki M, Syvalahti E, Hietala J.
Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor.
Psychopharmacology (Berl) 1996 Aug;126(3):234-40
"The present data provide evidence that fluoxetine, norfluoxetine and citalopram, along with many other antidepressant compounds, interact directly with the 5-HT2C receptor." [Abstract]
Gommans J, Bouwknecht JA, Hijzen TH, Berendsen HH, Broekkamp CL, Maes RA, Olivier B.
Stimulus properties of fluvoxamine in a conditioned taste aversion procedure.
Psychopharmacology (Berl) 1998 Dec;140(4):496-502
"We conclude that 5-HT1A receptors are involved in the stimulus properties of both fluvoxamine and fluoxetine, that 5-HT2C receptors are involved in fluvoxamine and especially fluoxetine, and, based primarily on the cross-comparison tests, that the two SSRIs have somewhat different stimulus properties." [Abstract]
Lightowler S, Wood M, Brown T, Glen A, Blackburn T, Tulloch I, Kennett G.
An investigation of the mechanism responsible for fluoxetine-induced hypophagia in rats.
Eur J Pharmacol 1996 Jan 25;296(2):137-43
"In slices of piglet choroid plexus fluoxetine (1, 10 and 33 microM) caused a rightward shift in the dose-response curve produced by 5-HT with no effect on the maximal response, and a mean pKB of 5.94 +/- 0.09. Norfluoxetine (10 microM) also produced a rightward shift in the 5-HT dose-response curve with no effect on the maximal response, and a pKB of 6.20. Thus, both compounds acted as surmountable antagonists with no agonist efficacy at 5-HT2C receptors present in choroid plexus." [Abstract]
Olivier B, van Oorschot R, Waldinger MD.
Serotonin, serotonergic receptors, selective serotonin reuptake inhibitors and sexual behaviour.
Int Clin Psychopharmacol 1998 Jul;13 Suppl 6:S9-14
"It appeared that the discriminatory stimulus of fluvoxamine is primarily mediated via 5-hydroxytryptamine (HT)1A receptors, whilst that of fluoxetine is primarily mediated via 5-HT2C receptors. Both types of receptors have been implicated in depression and it is conceivable that different SSRIs have intrinsic activity at these receptors." [Abstract]
Ward RP, Dorsa DM.
Colocalization of serotonin receptor subtypes 5-HT2A, 5-HT2C, and 5-HT6 with neuropeptides in rat striatum.
J Comp Neurol 1996 Jul 1;370(3):405-14
"All the serotonin receptors colocalized extensively with all three of the neuropeptides examined. None of the serotonin receptors showed preferential colocalization in striatopallidal (enkephalin containing), or striatonigral (substance P or dynorphin containing) cells. The 5-HT2A and 5-HT2C mRNAs displayed a differential distribution with regard to the scattered islands of strongly dynorphin mRNA positive cells, which are thought to reside in the striatal patch compartment. Within these islands, 5-HT2C mRNA expression was much higher than in surrounding areas. 5-HT2A mRNA showed the opposite pattern with decreased expression over dynorphin rich cell clusters." [Abstract]