5-HT1D receptor

5-hydroxytryptamine (serotonin) receptor 1D, also known as HTR1D, is a 5-HT receptor, but also denotes the human gene encoding it. 5-HT_1D acts on the central nervous system, and affects locomotion and anxiety. It also induces vasoconstriction in the brain.

Tissue distribution

5HT_1D receptors are found at low levels in the basal ganglia (globus pallidus, substantia nigra, caudate putamen), the hippocampus, and in the cortex.

Structure

5HT_1D 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_1D 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_1D receptor. The gene has been localized on chromosome 1, region 1p34.3-36.3

Ligands

Agonists

Molecular modelling has provided a picture of the agonistic binding site of 5HT_1D. The amino acid residues within the receptor binding site region have been identified. This is a valuable guide to design potential 5HT_1D receptor agonists. When sumatriptan binds there is major conformational change in both ligand and receptor in the binding pocket.

• 5-(Nonyloxy)tryptamine
• Sumatriptan (vasoconstrictor in migraine)
• Ergotamine (vasoconstrictor in migraine)
• Zolmitriptan
• 5-Carboxamidotryptamine (5-CT)
• 5-(t-Butyl)-N-methyltryptamine
• CP-135807
• CP-286601
• PNU-109291 ((S)-3,4-Dihydro-1-[2-[4-(4-methoxyphenyl)-1-piperazinyl]ethyl]-N-methyl-1H-2-benzopyran-6-carboxamide)
• PNU-142633 ((1S)-1-[2-[4-[4-(Aminocarbonyl)phenyl]-1-piperazinyl]ethyl]-3,4-dihydro-N-methyl-1H-2-benzopyran-6-carboxamide)
• GR-46611 (3-[3-(2-Dimethylaminoethyl)-1H-indol-5-yl]-N-(4-methoxybenzyl)acrylamide)
• L-694247 (2-[5-[3-(4-Methylsulfonylamino)benzyl-1,2,4-oxadiazol-5-yl]-1H-indol-3-yl]ethanamine)
• L-760790
• L-772405

Antagonists

• Ziprasidone (atypical antipsychotic) [1]
• Methiothepin (antipsychotic)
• Yohimbine (aphrodisiac)
• Metergoline
• BRL-15572
• Vortioxetine (antidepressant)
• GR-127935 (mixed 5-HT_1B/1D antagonist)
• LY-310762
• LY-367642
• LY-456219
• LY-456220

See also

• 5-HT₁ receptor
• 5-HT receptor

External links

• Human HTR1D genome location and HTR1D gene details page in the UCSC Genome Browser.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.