Disease relevance of Htr2c

• Baculovirus expression yielded high levels of 5-HT2C receptors (up to 10(6) receptors/cell), which were functionally coupled to polyphosphoinositide turnover in Sf9 cells through a pertussis toxin-insensitive pathway [1].
• However, pretreatment with mesulergine (a 5-HT2C/5-HT2A antagonist) significantly attenuated DOM-induced hyperthermia but not hypophagia [2].
• We suggest that trazodone (5, 10 and 20 mg/kg), by blocking the 5-HT 2C receptors, releases the nigrostriatal DAergic neurons from tonic inhibition caused by 5-HT, and thereby potentiates dexamphetamine stereotypy and antagonizes haloperidol catalepsy [3].
• 5-HT2C receptor involvement in female rat lordosis behavior [4].
• Our results suggest that hyperglycemia elicited by mCPP is mediated by 5-HT2C and/or 2B receptors, and in turn adrenomedullary catecholamine release, whereas that elicited by DOI involves 5-HT2A receptors [5].

Psychiatry related information on Htr2c

• Results suggest that 5-HT2A receptors and 5-HT2C receptors would play a crucial role in the development of myoclonia and locomotor activity, respectively [6].
• Reinforced spatial alternation as an animal model of obsessive-compulsive disorder (OCD): investigation of 5-HT2C and 5-HT1D receptor involvement in OCD pathophysiology [7].
• Taken together with the previous effects of SB 200646A in the rat social interaction test, this is compelling evidence that 5-HT2C/2B receptor antagonists may possess anxiolytic properties [8].
• Similarities in the action of Ro 60-0175, a 5-HT2C receptor agonist and d-fenfluramine on feeding patterns in the rat [9].
• The effects of repeated unpredictable mild stress (a regimen known to induce an anhedonic state in the rat) and of chronic administration of either of two recognized antidepressant treatments (sleep deprivation or inhibition of monoamine oxidase type A) in rats were studied on a 5HT1C receptor initiated response, i.e. mCPP-induced penile erection [10].

High impact information on Htr2c

• Moreover, we have identified a brain-specific small RNA, termed MBII-52, which was predicted to function as a nucleolar C/D RNA, thereby targeting an A-to-I editing site (C-site) within the 5-HT2C serotonin receptor pre-mRNA for 2'-O-methylation [11].
• A complementary DNA (cDNA) encoding a serotonin receptor with 51% sequence identity to the 5HT-1C subtype was isolated from a rat brain cDNA library by homology screening [12].
• The nigrostriatal dopamine system: a neglected target for 5-HT2C receptors [13].
• The effect of the 5-HT2A /2C receptor agonist on BDNF mRNA in both the hippocampus and the neocortex was blocked by pretreatment with a selective 5-HT2A, but not 5-HT2C, receptor antagonist [14].
• Differential actions of serotonin, mediated by 5-HT1B and 5-HT2C receptors, on GABA-mediated synaptic input to rat substantia nigra pars reticulata neurons in vitro [15].

Chemical compound and disease context of Htr2c

• Evidence that m-chlorophenylpiperazine-induced hyperthermia in rats is mediated by stimulation of 5-HT2C receptors [16].
• Only high doses of ketanserin, LY-53857 and ritanserin (5-HT2A/5-HT2C antagonists) as well as spiperone (5-HT1A/5-HT2A/D2 antagonist) attenuated m-CPP-induced hyperthermia [16].
• In contrast, pretreatment with metergoline (a 5-HT1/5-HT2 antagonist) and ritanserin (a 5-HT2A/5-HT2C antagonist) significantly attenuated both DOM-induced hypophagia and hyperthermia [2].
• Either of the antidepressants given repeatedly antagonized TFMPP-induced hyperthermia (another putative 5-HT2C effect) [17].
• The 5-HT2C/2B receptor agonist m-chlorophenylpiperazine (mCPP) inhibits 2-deoxy-D-glucose (2-DG)-induced hyperphagia in rats [18].

Biological context of Htr2c

• Mutagenesis analysis of the serotonin 5-HT2C receptor and a Caenorhabditis elegans 5-HT2 homologue: conserved residues of helix 4 and helix 7 contribute to agonist-dependent activation of 5-HT2 receptors [19].
• The 5-HT and 5-HT2C receptor kinetics were studied in cerebral cortex and brain stem of sham operated, 72 h pancreatectomised and 7 days pancreatectomised rats [20].
• Antagonist treatment of intact Sf9 cells or membranes containing the 5-HT2C receptor, followed by washout of residual drug, resulted in a decrease (up to 90%) in the number of binding sites for [3H]mesulergine and [3H]5-HT, with no change in the affinity for [3H]mesulergine [1].
• Thus, the up-regulation of 5-HT1B, 5-HT2A and possibly 5-HT2C receptors accompanying the 5-HT hyperinnervation after neonatal but not after adult dopamine denervation was associated with increased responsiveness (IT50) of neostriatal neurons to iontophoresed 5-HT and its receptor agonists [21].
• However, N-desmethylclozapine (10 microm), a selective 5-HT2C receptor antagonist, did not block the facilitation of the EPSP induced by alpha-methyl-5-HT [22].

Anatomical context of Htr2c

• According to this model, the excitation of GABAergic interneurons through these 5-HT2C (and also 5-HT2A) receptors would result in the suppression of 5-HT cell firing [23].
• Decreased 5-HT2C receptor binding in the cerebral cortex and brain stem during pancreatic regeneration in rats [20].
• Expression of serotonin 5-HT2C receptors in GABAergic cells of the anterior raphe nuclei [23].
• Insulin signaling inhibits the 5-HT2C receptor in choroid plexus via MAP kinase [24].
• This effect of antagonists in membranes was dose dependent, but the rank order of potency was clearly different from that for inverse agonist activity, indicating that the two effects reflect distinct actions of antagonists at the 5-HT2C receptor [1].

Associations of Htr2c with chemical compounds

• A K4.45M mutation decreased serotonin-dependent activity (Emax) of the rat 5-HT2C receptor by 60% and that of the C. elegans homologue by 40%, as determined by a fluorometric plate-based calcium assay [19].
• Modulation of dopamine release by striatal 5-HT2C receptors [25].
• Ketanserin (1) is a fairly selective 5-HT2 antagonist that binds both at 5-HT2A and 5-HT2C receptors [26].
• Furthermore, to determine which serotonergic receptor subtype may mediate this effect, the 5-HT2A receptor antagonist M100907 (formerly MDL 100,907) and the 5-HT2C receptor antagonist SDZ SER 082 were tested against dizocilpine [27].
• Seven receptor antagonists, endowed with relative selectivities for the 5-HT2A, 5-HT2B, and 5-HT2C subtypes, differentially affected the inhibition by (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane of the cyclic GMP response, suggesting that the receptor involved belongs to the 5-HT2C subtype [28].

Regulatory relationships of Htr2c

• 5-HT2C receptors inhibit and 5-HT1A receptors activate the generation of spike-wave discharges in a genetic rat model of absence epilepsy [29].

Other interactions of Htr2c

• These results suggest that 5-HT2 receptors have potential significance in brain development, with a functional difference between 5-HT2A and 5-HT2C receptor subtypes [30].
• In contrast, 5-HT2C receptor mRNA was found in most GABAergic cells, recognized by the presence of glutamic acid decarboxylase mRNA [23].
• Furthermore, both acute and chronic administration of selective 5-HT1A and 5-HT2C receptor agonists produce consistent increases in the number of newly formed neurons in the DG and/or olfactory bulb, underscoring the beneficial effects of 5-HT on adult neurogenesis [31].
• Role of 5-HT3 and 5-HT2C receptors located within the medial amygdala in the control of salt intake in sodium-depleted rats [32].
• Thus, serotonin can both depolarize and disinhibit SNr neurons via 5-HT2C and 5-HT1B receptors, respectively, but excitation may be limited by GABA released from axon collaterals [15].

Analytical, diagnostic and therapeutic context of Htr2c

• The functional significance of these class-specific substitutions was tested by site-directed mutagenesis of two distantly related 5-HT2 receptors, Caenorhabditis elegans 5-HT2ce and rat 5-HT2C [19].
• Unique expression patterns of 5-HT2A and 5-HT2C receptors in the rat brain during postnatal development: Western blot and immunohistochemical analyses [30].
• The present work utilized in vivo microdialysis to investigate the modulation of DA release by 5-HT2C receptors localized in the nerve terminal regions of the mesocortical and nigrostriatal DA pathways [25].
• We have used double in situ hybridization to examine the cellular localization of 5-HT2C receptor mRNA in relation to serotonergic and GABAergic neurons in the anterior raphe nuclei of the rat [23].
• The purpose of this study was to investigate the role of central 5-HT2C receptor binding in rat model of pancreatic regeneration using 60-70% pancreatectomy [20].

References