Alpha-4 beta-2 nicotinic receptor
The alpha-4 beta-2 nicotinic receptor, also known as the α4β2 receptor, is a type of
permeability.Stimulation of this receptor subtype is also associated with
addictive properties.[5]
The receptors exist in the two stoichiometries:
- (α4)2(β2)3 receptors have high sensitivity to Ca2+permeability (HS receptors)
- (α4)3(β2)2 receptors have low sensitivity to nicotine and high Ca2+permeability (LS receptors)
Structure
The α4β2 receptor assemble in two distinct stoichiometric forms. One stoichiometry contains three α4 and two β2 subunits [ (α4)3(β2)2 ] whereas the other stoichiometry contains two α4 and three β2 [ (α4)2(β2)3 ]. The x-ray structure of the (α4)2(β2)3 receptor is known since 2016[6] and reveals a circular α–β–β–α–β ordering of subunits.
Ligands
Source:[7]
Agonists
- 3-Bromocytisine
- Acetylcholine
- Cytisine
- Galantamine
- Epibatidine
- Epiboxidine[8]
- Nicotine
- A-84,543
- A-366,833
- ABT-418
- Arecoline[9]
- Altinicline
- Dianicline
- Ispronicline
- Pozanicline
- Rivanicline
- Tebanicline
- TC-1827
- Varenicline
- Sazetidine A: full agonist on (α4)2(β2)3, 6% efficacy on (α4)3(β2)2[10]
- N-(3-pyridinyl)-bridged bicyclic diamines[11][12][13]
PAMs
- NS-9283: 60-fold left-shifting of concentration-response curve, no change in maximum efficacy[14]
- Desformylflustrabromine[15]
- Further compounds.. (see references →)[16][17]
Antagonists
- (−)-7-methyl-2-exo-[3'-(6-[18F]fluoropyridin-2-yl)-5'-pyridinyl]-7-azabicyclo[2.2.1]heptane[18]
- 2-fluoro-3-(4-nitro-phenyl)deschloroepibatidine[19]
- Coclaurine - alkaloid from Nelumbo nucifera[20]
- Mecamylamine[21]
- α-Conotoxin
- PNU-120,596
- Bupropion
- Dihydro-β-erythroidine, selective[9]
- Nitrous oxide
- Isoflurane
- 1-(6-(((R,S)-7-Hydroxychroman-2-yl)methylamino]hexyl)-3-((S)-1-methylpyrrolidin-2-yl)pyridinium bromide (compound 2) (heterobivalent ligand: D2R agonist and nAChR antagonist)[22]
NAMs
See also
References
- PMID 10838608. Archived from the original(PDF) on 2014-05-15. Retrieved 2012-10-08.
- ^ ISBN 978-0-443-07145-4.
- PMID 18042647.
- PMID 28607947.
- ^ "Nicotine: Biological activity". IUPHAR/BPS Guide to Pharmacology. International Union of Basic and Clinical Pharmacology. Retrieved 7 February 2016.
Kis as follows; α2β4=9900nM [5], α3β2=14nM [1], α3β4=187nM [1], α4β2=1nM [4,6]. Due to the heterogeneity of nACh channels we have not tagged a primary drug target for nicotine, although the α4β2 is reported to be the predominant high affinity subtype in the brain which mediates nicotine addiction [2-3].
- PMID 27698419.
- PMID 37302724.
- PMID 22566097.
- ^ PMID 34417356.
- S2CID 24632914.
- PMID 17585748.
- PMID 17181167.
- PMID 17929796.
- PMID 23278456.
- PMID 17604168.
- PMID 18789861.
- PMID 18805006.
- PMID 18605717.
- S2CID 96557182.
- PMID 15598565.
- S2CID 31849794.
- PMID 26164842.
- PMID 22064677.