5HT5

5-HT5, or the 5-HT5 receptor family, refers to a subclass of serotonin receptors in the 5-HT receptor family. In humans, two genes are associated with this family: HTR5A, which encodes the functional 5-HT5A receptor, and HTR5B, which is present in some species as a functional receptor but is a nonfunctional pseudogene in humans. The 5-HT5A receptor is a G protein-coupled receptor (GPCR) belonging to the rhodopsin-like subfamily and is predicted to have the standard seven transmembrane domains characteristic of GPCRs.

Signaling and function in cells: The 5-HT5A receptor couples primarily to Gi/o proteins, leading to inhibition of adenylyl cyclase and a decrease in intracellular cAMP levels. This signaling can influence neuronal excitability and downstream pathways, including potential effects on ion channels and various second-messenger systems. The 5-HT5B receptor, where functional (in species other than humans), is also a GPCR with similar coupling, but its relevance to human physiology is limited due to its pseudogene status in humans.

Expression and distribution: In humans, 5-HT5A expression has been detected in multiple brain regions, including the cerebral cortex, hippocampus, thalamus, and striatum, as well as in some peripheral tissues. The precise regional distribution and the functional significance of 5-HT5A signaling in these areas remain areas of active research.

Pharmacology and research tools: Compared with other 5-HT receptors, the pharmacology of 5-HT5A is less well developed. A number of small-molecule antagonists and inverse agonists have been described, but many lack strong selectivity or brain penetration, and no 5-HT5A-targeting drugs are approved for clinical use. Most functional insights come from animal studies or from experiments using less selective serotonin receptor ligands or genetic models.

Clinical relevance: The exact role of 5-HT5A signaling in human neurobiology and disease is not yet clear. Ongoing research seeks to define its contributions to mood, cognition, circadian regulation, and other neural processes. See also HTR5A gene.