HTR - 5-Hydroxytryptamine receptors | Elisa - Clia - Antibody - Protein

Background:

5-Hydroxytryptamine receptors, commonly known as serotonin receptors, are a class of G protein-coupled receptors and ligand-gated ion channels in the central and peripheral nervous systems. Serotonin, also known as 5-hydroxytryptamine (5-HT), is a neurotransmitter involved in various physiological functions, including mood regulation, sleep, appetite, and cognition.

Classification and Subtypes

5-HT receptors are part of the broader family of G protein-coupled receptors (GPCRs) and ligand-gated ion channels. The classification system primarily depends on molecular, pharmacological, and functional criteria. The seven main families include 5-HT1 to 5-HT7, each with multiple subtypes (e.g., 5-HT1A, 5-HT1B, 5-HT2A, etc.). Subtypes often exhibit distinct cellular and tissue distributions, coupling mechanisms to intracellular signaling pathways, and functional roles.

Structural and Molecular Characteristics

Crystallographic studies and computational modeling have provided insights into the three-dimensional structure of 5-HT receptors. These receptors typically consist of seven transmembrane helices (TM1-TM7), extracellular loops, and intracellular loops, with variations in their amino acid sequences determining subtype-specific properties. Understanding the receptor's structure is critical for rational drug design and the development of selective ligands.

Distribution and Localization

Serotonin receptors are widely distributed throughout the central and peripheral nervous systems, including the brain, spinal cord, and enteric nervous system. Different subtypes exhibit distinct patterns of expression within specific brain regions, neuronal populations, and peripheral tissues. For instance, 5-HT1A receptors are abundant in the raphe nuclei and limbic system, while 5-HT2A receptors are prevalent in the cortex and certain subcortical regions.

Physiological Functions

The diverse array of physiological functions modulated by serotonin receptors underscores their importance in homeostasis and behavior. Beyond classical roles in mood and emotion regulation, serotonin receptors influence cognition, memory, motor control, cardiovascular function, thermoregulation, endocrine secretion, and immune response. The complexity arises from the interactions between different receptor subtypes and their downstream signaling pathways within specific neural circuits and organ systems.

Mechanisms of Signaling

Upon serotonin binding, 5-HT receptors initiate signaling cascades through G protein-dependent or -independent mechanisms.G protein-coupled receptors typically activate or inhibit adenylate cyclase, leading to changes in cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) activation. Other signaling pathways include phospholipase C (PLC)-mediated production of inositol trisphosphate (IP3) and diacylglycerol (DAG), intracellular calcium release, and activation of protein kinase C (PKC).

Pharmacological

Pharmacotherapy targeting serotonin receptors represents a cornerstone of psychiatric and neurological treatments. Selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and atypical antipsychotics exert their therapeutic effects through modulation of serotoninergic neurotransmission. Clinical Implications and Pathologies: Dysregulation of serotonin signaling is implicated in various neuropsychiatric disorders, including major depressive disorder, anxiety disorders, bipolar disorder, schizophrenia, obsessive-compulsive disorder (OCD), and eating disorders. Genetic variations in serotonin receptor genes, alterations in receptor density or function, and disruptions in serotonin synthesis or metabolism contribute to disease susceptibility and treatment response heterogeneity. Preclinical and clinical studies continue to elucidate the underlying mechanisms and identify novel therapeutic targets for these conditions.