5-hydroxytryptamine (serotonin) receptor 1D, also known as HTR1D, is a 5-HT receptor, but also denotes the human gene encoding it. 5-HT<sub>1D</sub> acts on the central nervous system, and affects locomotion and anxiety. It also induces vasoconstriction in the brain.
5HT<sub>1D</sub> receptors are found at low levels in the basal ganglia (globus pallidus, substantia nigra, caudate putamen), the hippocampus, and in the cortex.
5HT<sub>1D</sub> receptor is a G protein linked receptor that activates an intracellular messenger cascade to produce an inhibitory response by decreasing cellular levels of cAMP. The 5HT<sub>1D</sub> is a 7-TM receptor. A large intercellular loop between TM-5 and TM-6 is believed to be associated with coupling to a second messenger. Agonists might bind in a manner that utilizes an aspartate residue in TM-3 and residues in the TM-4, TM-5 and TM-6. A human clone containing an intronless open reading frame was found to encode 377 amino acids of the 5HT<sub>1D</sub> receptor. The gene has been localized on chromosome 1, region 1p34.3-36.3
Molecular modelling has provided a picture of the agonistic binding site of 5HT<sub>1D</sub>. The amino acid residues within the receptor binding site region have been identified. This is a valuable guide to design potential 5HT<sub>1D</sub> receptor agonists. When sumatriptan binds there is major conformational change in both ligand and receptor in the binding pocket.