Disease relevance of HTR5A

• Human serotonin 5A (5-HT5A) receptors were stably expressed in undifferentiated C6 glioma [1].
• The 5-HT5A gene colocalized with the mouse mutation reeler and the human mutation holoprosencephaly type 3, which both result in abnormal brain development, raising the possibility that the 5-HT5A receptor plays a role in brain development [2].

Psychiatry related information on HTR5A

• We conclude that allelic variation in the human 5-HT5A receptor gene may be involved in susceptibility to schizophrenia and affective disorders but not in determining response to clozapine [3].
• Genetic variation in the 5-HT5A receptor gene in patients with bipolar disorder and major depression [4].

High impact information on HTR5A

• We propose that REC17 and MR22, designated as 5-HT5 alpha and 5-HT5 beta, represent a distinct subfamily of 5-HT receptors [5].
• Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase [6].
• An intronless gene encoding an additional human serotonin (5-HT) 5-HT1-like receptor subtype was isolated from a human genomic library with probes obtained from degenerate PCR primers used to amplify 5-HT-receptor-specific sequences [6].
• We also determined the chromosomal localization of the 5-HT5A and 5-HT5B genes and of their human counterparts [2].
• It was concluded that in addition to the inhibition of cAMP accumulation and ADP-ribosyl cyclase activity, 5-HT5A receptors regulate intracellular Ca2+ mobilization which is probably a result of the IP3-sensitive Ca2+ store [1].

Chemical compound and disease context of HTR5A

• When the 5-HT5A receptors were expressed in undifferentiated C6 glioma cells, they modulated the level of second messengers [7].

Biological context of HTR5A

• Assignment of the 5-hydroxytryptamine (serotonin) receptor 5A gene (HTR5A) to human chromosome band 7q36.1 [8].
• The deduced amino acid sequence of the gene reveals a protein of 357 residues which shares 93% (nucleotide) and 84% (amino acid) identity to the cloned mouse 5-HT5A receptor [9].
• As with the mouse and rat 5-HT5A receptors, the gene consists of two coding exons separated by a large intron [9].
• 5. A ligand-stimulated reduction in the detectable level of the catalytic domain of protein kinase A (PKA) in nuclear extracts isolated from Human 5-HT5A expressing cells was observed [10].
• Genetic variation in the 5-HT5A gene might be involved in susceptibility to depression, the major psychoses or in influencing clinical response to treatment [3].

Anatomical context of HTR5A

• Identification of one of the least well understood 5-HT receptors (5-HT5A) in the spinal cord [11].
• 4. A dose-dependent inhibition of cyclic AMP accumulation was observed in the recombinant Human 5-HT5A receptor cell line, suggesting a functional coupling to a G alpha i, G-protein in the HEK-293 cell line [10].
• Our results showed that the main sites of 5-HT5A mRNA expression were the cerebral cortex, hippocampus and cerebellum [12].
• The broad distribution in the neocortex and hippocampus supports the view that the 5-HT5A receptor in these areas might be implicated in high cortical and limbic functions [12].
• The 5-HT5A mRNA was widely distributed in the cerebellum where it was highly expressed in the Purkinje cells, in the dentate nucleus and, at a lower level, in the granule cells [12].

Associations of HTR5A with chemical compounds

• No interaction was encountered between 2-methyl-5-HT and MDL72222, suggesting an absence of 5-HT3 receptors [13].
• This action appears to be due to activation of a 5-HT1-like receptor as it is mimicked by some 5-HT1 receptor ligands (mCPP, TFMPP and 5-Me-O-DMT), but not by DOI (5-HT2) or 2-Me-5-HT (5-HT3) [14].
• These properties distinguish this receptor from any previously characterized and establish a fifth 5-HT1-like receptor subtype (5-HT1F) coupled to the inhibition of adenylate cyclase [6].
• On the other hand, activation of 5-HT5A receptors transiently opened the K+ channels, presumably due to the increase in intracellular Ca2+ after formation of inositol (1,4,5) trisphosphate [7].
• In addition to this known signaling via Gi/Go, 5-HT5A receptors are coupled to the inhibition of ADP-ribosyl cyclase and cyclic ADP ribose formation [7].

Other interactions of HTR5A

• The polymorphism studied for 5-HT5A, 5-HT6, alpha1A- and alpha2A-receptors give no clear associations with the response to clozapine [15].
• This review was undertaken to summarize the results of structure-activity relationship studies with ligands of 5-HT5, 5-HT6 and 5-HT7 receptors [16].
• This is the first study to describe such G-protein activation for the Human 5-HT5A receptor in any cell [10].
• Two polymorphisms (-19G/C and 12A/T) in the 5-HT5A receptor gene were analyzed by polymerase chain reaction amplification and subsequent enzyme digestion [4].

Analytical, diagnostic and therapeutic context of HTR5A

• Extensive fluorescence in situ hybridization analysis showed that the HPE3 critical gene region, inclusive Sonic hedgehog (SHH), En2 (HOX1), and HTR5A, was deleted [17].
• The detection of a frequent G-->C substitution at position -19 was used for fine scale linkage mapping of the 5-HT5A gene [18].

References