Human HTR4

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-HT4 receptor

The 5-HT4 receptor is a GPCR that couples via Gs to increase cAMP production. The structure displays less than 34% amino acid sequence identity to other 5-HT GPCRs justifying the separate family. At least 10 splice variants have been identified.PharmacologySelective agonists (e.g. RS 67506 [partial agonist]) and antagonists (e.g. SB 204070) are available.Clinical significance5-HT4 receptor agonists (e.g. cisapride, tegaserod) were effective drugs reducing the symptoms of gastro-oesophageal reflux, constipation and constipation-predominant irritable bowel syndrome (IBS-c), before they were withdrawn due to cardiovascular side-effects. [close]