Introduction of HTR5A
5-hydroxytryptamine receptor 5A (HTR5A), alternatively called serotonin receptor 5A, is a multi-pass membrane protein that belongs to the 5-hydroxytryptamine receptor family. Only the HTR5A subtype is expressed in human brain and it is encoded by HTR5A gene. Within the CNS (central nervous system), HTR5A shows a relatively broad distribution in human brain, including the cerebral cortex, thalamus, hypothalamus, hippocampus, habenula, cerebellum, and spinal cord. The HTR5A receptor has been supposed to be functional in a native expression system.
|Basic Information of HTR5A|
|Protein Name||5-hydroxytryptamine receptor 5A|
|Aliases||Serotonin receptor 5A, 5-HT-5, 5-HT-5A, 5-HT5A|
|Organism||Homo sapiens (Human)|
Function of HTR5A Membrane Protein
The 5-hydroxytryptamine (5-HT, also known as neurotransmitter serotonin) has been implicated in a wide range of psychiatric conditions and also has vasoconstrictive and vasodilatory effects. HTR5A receptor functions as a receptor for 5-hydroxytryptamine and couples to G proteins, negatively influencing cAMP levels via Gi and Go. This receptor has been supposed to function in part through the regulation of intracellular Ca2+ mobilization. HTR5A has been shown to be functional in a native expression system. It also appears to act as a presynaptic serotonin autoreceptor. Several studies have investigated the contribution of HTR5A receptor polymorphisms to the risk of bipolar and unipolar depression. A selective HTR5A receptor antagonist has been identified and has been shown to decrease 5-carboxyamidotryptamine-induced inhibition of raphe neuronal cell firing in vitro and to increase 5-HT levels in prefrontal cortex in vivo, suggesting a role for the 5-HT5A receptor in the modulation of raphe 5-HT neuronal activity.
Fig.1 Schematic model involving presynaptic 5-HT heteroreceptors (red). (Vinkers, 2010)
Application of HTR5A Membrane Protein in Literature
The results showed that ASP5736 might block the inhibitory 5-HT5A receptors on DAergic neurons in the VTA that projected to the mPFC, and interneurons in the mPFC, and thereby improved cognitive impairment by preferentially enhancing DAergic and GABAergic neurons in the mPFC.
The observations of this study revealed that the preclinical efficacy of a strategy based on the blockade of 5-HT5A receptors against schizophrenia-like cognitive deficits and negative symptoms.
This article showed that 5-HT5A receptors reduced pain processing in the spinal cord and that 5-HT and 5-CT reduced neuropathic pain through activation of 5-HT5A and 5-HT1A/1B/1D receptors.
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.
The findings suggested that variations of the two serotonin receptors subtypes supported their potential roles in obesity.
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