HTR2C Membrane Protein Introduction

Introduction of HTR2C

5-hydroxytryptamine receptor 2C (HTR2C), alternatively called serotonin receptor 2C, is a G protein-coupled receptor (GPCR) and belongs to the 5-HT2 receptor subfamily which binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). HTR2C is encoded by HTR2C gene in human and is coupled to Gq/G11 and mediates excitatory neurotransmission. HTR2C receptors are primarily found in the choroid plexus, and also expressed on epithelial cells lining the ventricles. This receptor exists as a homodimer at the cell surface.

Function of HTR2C Membrane Protein

The HTR2C receptor is one of the many binding sites for serotonin and belongs to the beta-arrestin family that inhibits signaling by G proteins and mediates activation of alternative signaling pathways. Like other 5-HT receptors, the binding of HTR2C and its ligands results in a conformation change that activates signaling through guanine nucleotide-binding proteins (G proteins) and regulates the activity of downstream effectors. HTR2C may regulate neuronal activity by the activation of short transient receptor potential calcium channels in the brain, and thus regulates the activation of proopiomelanocortin neurons and the release of CRH that then modulates the release of corticosterone. HTR2C is supposed to significantly regulate mood, anxiety, feeding, and reproductive behavior. Activation of HTR2C could inhibit dopamine and norepinephrine release in certain areas of the brain. Moreover, HTR2C is involved in insulin sensitivity and glucose homeostasis. Several studies have indicated that some suicide victims have an abnormally high number of HTR2C receptors in the prefrontal cortex.

Fig.1 Structure of HTR2C membrane protein.

Application of HTR2C Membrane Protein in Literature

1. Phillips B.U., et al. Selective effects of 5-HT2C receptor modulation on performance of a novel valence-probe visual discrimination task and probabilistic reversal learning in mice. Psychopharmacology (Berl). 2018, 235(7):2101-2111. PubMed ID: 29682701
   
   

   The results showed that 5-HT2CRs tightly regulated feedback sensitivity bias in mice with consequent effects on learning and cognitive flexibility and specified a framework for the influence of 5-HT2CRs on sensitivity to reinforcement.

2. Hankosky E.R. Age- and sex-dependent effects of methamphetamine on cognitive flexibility and 5-HT2C receptor localization in the orbitofrontal cortex of Sprague-Dawley rats. Behav Brain Res. 2018, 349:16-24. PubMed ID: 29715538
   
   

   The observations of this study revealed that age and sex differences in drug-induced deficits in reversal learning and 5-HT2CR co-localization with parvalbumin interneurons were dissociable and can manifest independently.

3. Ouchi M., et al. Effect of a 5-HT2c receptor agonist on urethral closure mechanisms in female rats. Neurourol Urodyn. 2018. PubMed ID: 29624732
   
   

   This article showed that 5-HT2c receptors agonists may have dual effects in patients with SUI (stress urinary incontinence), not only by reducing obesity but also by enhancing active urethral closure.

4. Tavares L.R.R., et al. Activation of 5-HT2C (but not 5-HT1A) receptors in the amygdala enhances fear-induced antinociception: Blockade with local 5-HT2C antagonist or systemic fluoxetine. Neuropharmacology. 2018, 135:376-385. PubMed ID: 29548885
   
   

   The findings of this study indicated that 5-HT may facilitate nociception and intensified OAA (arm-induced antinociception), respectively, at 5-HT1A and 5-HT2C receptors located in the amygdala of mice.

5. Faton S., et al. 5-HT2C receptors in the ventral tegmental area, but not in the arcuate nucleus, mediate the hypophagic and hypolocomotor effects of the selective 5-HT2C receptor agonist AR231630 in rats. Behav Brain Res. 2018, 347:234-241. PubMed ID: 29555337
   
   

   Authors of this study suggested that 5-HT2C receptor in the VTA (ventral tegmental area), but not in the ARC (arcuate nucleus), participated in both homeostatic and hedonic food intake and brain reward function.

HTR2C Preparation Options

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