Human HTR1A

5-Hydroxytryptamine receptors

5-HT receptors are, with the exception of the ionotropic 5-HT₃ class, GPCRs where the endogenous agonist is 5-hydroxytryptamine. The diversity of metabotropic 5-HT receptors is increased by alternative splicing... [read more] that produces isoforms of the 5-HT_2A (non-functional), 5-HT_2C (non-functional), 5-HT₄, 5-HT₆ (non-functional) and 5-HT₇ receptors. Unique amongst the GPCRs, RNA editing produces 5-HT_2C receptor isoforms that differ in function, such as efficiency and specificity of coupling to G_q/11 and also pharmacology [1,2]. Most 5-HT receptors (except 5-ht_1e and 5-ht_5b) play specific roles mediating functional responses in different tissues (reviewed by [3,4]).

References

1. Bockaert J, Claeysen S, Bécamel C, et al. Neuronal 5-HT metabotropic receptors: fine-tuning of their structure, signaling, and roles in synaptic modulation. Cell Tissue Res 2006;326:553-72.
2. Werry TD, Loiacono R, Sexton PM, et al. RNA editing of the serotonin 5HT2C receptor and its effects on cell signalling, pharmacology and brain function. Pharmacol Ther 2008;119:7-23.
3. Villalón CM, Centurión D. Cardiovascular responses produced by 5-hydroxytriptamine:a pharmacological update on the receptors/mechanisms involved and therapeutic implications. Naunyn Schmiedebergs Arch Pharmacol 2007;376:45-63.
4. Ramage AG, Villalón CM. 5-hydroxytryptamine and cardiovascular regulation. Trends Pharmacol Sci 2008;29:472-81.

5-HT1 receptors

The 5-HT1 receptor family comprises five different receptors (5-HT1A, 5-HT1B, 5-HT1D, 5-ht1e, 5-HT1F), which share 40-63% amino acid sequence identity and can couple to Gi/Go to inhibit cAMP formation, although signaling via other transduction systems are known (e.g. 5-HT1A receptor activates G-protein-gated inwardly rectifying K+ channel [GIRK]). One of the 5-HT1 receptor class, the 5-ht1e receptor, is yet to achieve receptor status since a robust response mediated via the protein is yet to be reported in the literature; lower-case appellation is used to denote this. 5-HT1A and 5-HT1B receptors act as somatodendritic and terminal autoreceptors, respectively; however, these receptors are also expressed throughout the CNS.PharmacologyA number of well-defined selective agonists (e.g. 8-OH-DPAT [5-HT1A receptor], PNU 109291 [5-HT1D receptor], LY 344864 [5-HT1F receptor]) and antagonists (e.g. WAY100635 [5-HT1A receptor], SB236057 [5-HT1B receptor], SB714786 [5-HT1D receptor]), are available to selectively probe some individual members of the 5-HT1 receptors.Clinical significance5-HT1A receptors are targeted by the anxiolytic drug, buspirone, which is a partial agonist. Various ‘triptans’ (e.g. sumitriptan and zolmitriptan) are used to treat acute migraine attack, these drugs are 5-HT1B/5-HT1D receptor agonists, with some also having agonist activity at the 5-HT1F receptor. [close]