HTR7 Membrane Protein Introduction

Introduction of HTR7

HTR7 belongs to the G protein-coupled serotonin receptor family which has seven transmembrane domains. It is encoded by HTR7 gene and exists three different splice variants with different carboxy terminals. The receptor couples with Gs subunit of cell surface involving in regulating the production of intracellular signaling molecule cAMP and multiple signaling pathway transductions. Recently, a lot of studies indicate that the receptor can be used as a drug development target for the treatment of several clinical disorders, such as neuromodulation disorder, mental disorders.

Function of HTR7 Membrane Protein

Activated HTR7 by binding to its ligands (serotonin, a biogenic neurotransmitter and hormone) can stimulate the activation of adenylate cyclase, thus increasing the production of intracellular second messenger cAMP. The receptor is especially expressed in the brain areas, such as hippocampus, hypothalamus, and cortex. It can increase the density of dendritic spines and promote synaptogenesis in forebrain neurons and regulate neurotransmission. Previous studies have indicated that HTR7 is involved in regulating a variety of biological processes, including thermoregulation, circadian rhythm, mood, learning and memory, and sleep. Hence, HTR7 may be a potential drug target for the treatment of several clinical disorders, such as cognitive disturbances, sleep and circadian rhythmicity disorders, anxiety and depression. And HTR7 antagonists might be used to treat the cognitive definitive deficits and mood disorders. Besides, recent findings show that HTR7 also regulates inflammatory response. For example, HTR7 regulates inflammatory fibrotic process induced by chronic liver injury and 5-HT7 agonist may protect liver tissue from liver fibrosis. HTR7 also plays a critical role in acute and chronic inflammation of the gastrointestinal tract. In addition, some studies show that the functions of HTR7 are required in regulating mammary epithelial structure and function, thus providing a new therapeutic target for mastitis and breast cancer treatment.

Fig.1 Stimulation of HTR7: schematic drawing of signaling pathways and downstream effectors leading to remodeling of neuronal morphology conservation. (Volpicelli F, 2014)

Application of HTR7 Membrane Protein in Literature

1. Shahidi S., et al. The effect of chronic stimulation of serotonin receptor type 7 on recognition, passive avoidance memory, hippocampal long-term potentiation, and neuronal apoptosis in the amyloid β protein treated rat. Psychopharmacology. 2018, 235(5):1513-1525. PubMed ID: 29637287
   
   

   The study shows that 5-HTR7 agonist can reduce amyloid beta (Aβ) plaque accumulation and neuronal apoptosis, thereby improving cognition and memory performance. So the 5-HTR7 agonist, AS19, may be a useful therapeutic drug for Alzheimer's disease.

2. Carbone C., et al. Activation of 5-HT7 receptor by administration of its selective agonist, LP-211, modifies explorative-curiosity behavior in rats in two paradigms which differ in visuospatial parameters. Cns Neuroscience & Therapeutics. 2018. PubMed ID: 29392842
   
   

   The study suggests that the selective agonist, LP-211 can activate 5-HT7 receptor, thereby regulating explorative-curiosity behavior in rats with differing in visual and spatial memory.

3. Arreola-Peralta L.D., et al. Potentiation of capsaicin-induced neurogenic inflammation by 5-HT7 receptors in the rat hind paw: involvement of calcitonin gen-related peptide. Peptides. 2018, 105:1-6. PubMed ID: 29730242
   
   

   The research indicates that sensitization of capsaicin-sensitive primary sensory neurons by 5-HT7 receptors may result in facilitation of neurogenic inflammation involving calcitonin gene-related peptide (CGRP) in the rat hind paw.

4. Wang M., et al. Effect of exosome biomarkers for diagnosis and prognosis of breast cancer patients. Clinical & Translational Oncology. 2018, 20(7): 906-911. PubMed ID: 29143228
   
   

   The study indicates that exosome biomarkers can be used for early diagnosis and prognosis of breast cancer patients in clinic. And exosome-carrying TRPC5, NANOG, NEUROD1, HTR7, KISS1R, and HOXC are related to progression-free survival (PFS), overall survival (OS) or disease-free survival (DFS) in breast cancer.

5. Yu O., et al. Serotonin 5-HT7 receptor in the ventral hippocampus modulates the retrieval of fear memory and stress-induced defecation. International Journal of Neuropsychopharmacology. 2016, 19(6):1-12. PubMed ID: 26647382
   
   

   The study shows that 5-HT7 receptor in the ventral hippocampus is involved in the mediation of retrieval of fear memory and stress-induced defecation. 5-HT7 receptor might be used as a drug target for treating mental disorders involving fear memory and gastrointestinal problems.

HTR7 Preparation Options

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Reference

1. Volpicelli F, et al. (2014). The serotonin receptor 7 and the structural plasticity of brain circuits. Frontiers in Behavioral Neuroscience, 8(6), 1-6.

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