5-HT1B receptor

5-hydroxytryptamine receptor 1B also known as the 5-HT_1B receptor is a protein that in humans is encoded by the HTR1B gene. The 5-HT_1B receptor is a 5-HT receptor subtype.

Tissue distribution and function

5-HT_1B receptors are widely distributed throughout the central nervous system with the highest concentrations found in the frontal cortex, basal ganglia, striatum, and the hippocampus. The function of the 5-HT_1B receptor differs depending upon its location. In the frontal cortex, it is believed to act as a terminal receptor inhibiting the release of dopamine. In the basal ganglia and the striatum, evidence suggests 5-HT signaling acts on an autoreceptor, inhibiting the release of serotonin and decreasing glutamatergic transmission by reducing miniature excitatory postsynaptic potential (mEPSP) frequency, respectively. In the hippocampus, a recent study has demonstrated that activation of postsynaptic 5-HT_1B heteroreceptors produces a facilitation in excitatory synaptic transmission which is altered in depression. When the expression of 5-HT_1B in human cortex was traced throughout life, significant changes during adolescence were observed, in a way that is strongly correlated with the expression of 5-HT_1E.

Outside of the CNS, the 5-HT_1B receptor is also expressed on the endothelium of blood vessels, particularly in the meninges. Activation of these receptors results in vasoconstriction. The high distribution of vasoconstrictive 5-HT_1B and 5-HT_1D receptors around the brain makes them a valuable drug target for the treatment of migraines.

Blocking 5-HT_1B receptor signalling also increases the number of osteoblasts, bone mass, and the bone formation rate.

Knockout mice lacking the 5-HT_1B gene have been reported to have a higher preference for alcohol, although later studies failed to replicate such abnormalities in alcohol consumption. These mice have also been reported to have a lower measure of anxiety (such as on the elevated plus maze test) and a higher measure of aggression.

Under basal conditions, knockout mice present with a "normal" phenotype and exhibit a sucrose preference (lack of sucrose preference is considered a measure of anhedonia). However, after undergoing chronic unpredictable stress treatment to induce a "depression-like" phenotype these animals do not benefit from administration of selective serotonin reuptake inhibitor (SSRIs).

Activation of the serotonin 5-HT_1B receptor appears to mediate the prosocial effects of entactogens acting as serotonin releasing agents like MDMA in animals. In addition, serotonin 5-HT_1B receptor activation appears to mediate the locomotor hyperactivity of these agents. The serotonin 5-HT_1B receptor also appears to be required for the persisting antidepressant- and anxiolytic-like effects as well as acute hypolocomotion of the serotonergic psychedelic and non-selective serotonin receptor agonist psilocybin in animals.

Ligands

Agonists

• 2ZEDMA (also a 5-HT_2A agonist)
• 5-Carboxamidotryptamine (5-CT)
• 5-MAPB
• 5-MAPBT
• 6-MAPB
• 6-MAPBT
• Almotriptan
• Anpirtoline (D-16949)
• Avitriptan
• Batoprazine
• BK-5-MAPB
• BK-5-MAPBT
• BK-6-MAPB
• CGS-12066A
• CP-93,129 (peripherally acting)
• CP-94,253
• CP-122,288 (mixed 5-HT_1B/1D agonist)
• CP-135,807 (mixed 5-HT_1B/1D agonist)
• Dihydroergotamine
• Donitriptan
• Eletriptan
• Eltoprazine (DU-28853)
• Emodin-8-glucoside
• Ergotamine
• Fluprazine
• Frovatriptan
• L-741604
• Lisuride
• mCPP
• MDMA
• Methylergometrine (methylergonovine)
• Methylone
• Methysergide
• Naratriptan
• Oxymetazoline
• Pergolide
• PZKKN-94 (also a 5-HT₆ antagonist)
• Rizatriptan
• RU-24969 (mixed 5-HT_1A/1B agonist)
• (S)-DCPT
• Serotonin
• Sumatriptan
• TFMPP
• Tryptamine psychedelics (e.g., 5-MeO-DMT, DPT, psilocin/psilocybin)
• Zolmitriptan

Partial agonists

• Asenapine
• AZ10419369
• Bromocriptine
• Metergoline
• Naphthylpiperazine
• Vortioxetine
• Ziprasidone

Antagonists and inverse agonists

• Alprenolol
• AOP-208 (LB-208)
• AR-A000002 (AZD-8129)
• Aripiprazole
• AZD-1134
• AZD-3783
• AZ12320927
• Carteolol
• Elzasonan
• GR-55562
• GR-127935
• Isamoltane (CGP-361A)
• LY-393558
• Metitepine (methiothepin)
• NAS-181 (MCOMM)
• Oxprenolol
• Penbutolol
• Propranolol
• Risperidone
• SB-216,641
• SB-224,289 (inverse agonist)
• SB-236,057 (inverse agonist)
• SB-245,570
• SB-649,915
• Tertatolol
• Yohimbine

Unknown

• Dextromethorphan

Genetics

In humans the protein is coded by the gene HTR1B.

A genetic variant in the promoter region, A-161T, has been examined with respect to personality traits and showed no major effect.

See also

• 5-HT₁ receptor
• 5-HT receptor

External links

• Human HTR1B genome location and HTR1B gene details page in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: P28222 (5-hydroxytryptamine receptor 1B) at the PDBe-KB.

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