ArticleBiochemistry2012
Bupropion binds to two sites in the Torpedo nicotinic acetylcholine receptor transmembrane domain: a photoaffinity labeling study with the bupropion analogue [(125)I]-SADU-3-72.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- A bupropion modulatory site in the Gloeobacter violaceus ligand-gated ion channel.Biophysical journal · 2024Article
- Identification of a binding site for bupropion inbioRxiv : the preprint server for biology · 2023Article
- New medications development for smoking cessation.Addiction neuroscience · 2023Article
- Bupropion Inhibits Serotonin Type 3AB Heteromeric Channels at Clinically Relevant Concentrations.Molecular pharmacology · 2020Article
- Enantiomeric barbiturates bind distinct inter- and intrasubunit binding sites in a nicotinic acetylcholine receptor (nAChR).The Journal of biological chemistry · 2017Article
- The antidepressant bupropion is a negative allosteric modulator of serotonin type 3A receptors.Neuropharmacology · 2017Article
- Mutational Analysis at Intersubunit Interfaces of an Anionic Glutamate Receptor Reveals a Key Interaction Important for Channel Gating by Ivermectin.Frontiers in molecular neuroscience · 2017Article
- Review
- Functional Chimeras of GLIC Obtained by Adding the Intracellular Domain of Anion- and Cation-Conducting Cys-Loop Receptors.Biochemistry · 2015Article
- Intramembrane aromatic interactions influence the lipid sensitivities of pentameric ligand-gated ion channels.The Journal of biological chemistry · 2015Article
- The Effect of Acute Intra Locus Coeruleus (LC) Microinfusion of Bupropion on Formalin-Induced Pain Behavior in Rat.Basic and clinical neuroscience · 2014Article
- Smoking behaviour and mental health disorders--mutual influences and implications for therapy.International journal of environmental research and public health · 2013Review
- Inhibition versus potentiation of ligand-gated ion channels can be altered by a single mutation that moves ligands between intra- and intersubunit sites.Structure (London, England : 1993) · 2013Article
- Structural sensitivity of a prokaryotic pentameric ligand-gated ion channel to its membrane environment.The Journal of biological chemistry · 2013Article
- Development of novel pharmacotherapeutics for tobacco dependence: progress and future directions.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2012Review
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Bupropion, a clinically used antidepressant and smoking-cessation drug, acts as a noncompetitive antagonist of nicotinic acetylcholine receptors (nAChRs). To identify its binding site(s) in nAChRs, we developed a photoreactive bupropion analogue, (±)-2-(N-tert-butylamino)-3'-[(125)I]-iodo-4'-azidopropiophenone (SADU-3-72). Based on inhibition of [(125)I]SADU-3-72 binding, SADU-3-72 binds with high affinity (IC(50) = 0.8 μM) to the Torpedo nAChR in the resting (closed channel) state and in the agonist-induced desensitized state, and bupropion binds to that site with 3-fold higher affinity in the desensitized (IC(50) = 1.2 μM) than in the resting state. Photolabeling of Torpedo nAChRs with [(125)I]SADU-3-72 followed by limited in-gel digestion of nAChR subunits with endoproteinase Glu-C established the presence of [(125)I]SADU-3-72 photoincorporation within nAChR subunit fragments containing M1-M2-M3 helices (αV8-20K, βV8-22/23K, and γV8-24K) or M1-M2 helices (δV8-14). Photolabeling within βV8-22/23K, γV8-24K, and δV8-14 was reduced in the desensitized state and inhibited by ion channel blockers selective for the resting (tetracaine) or desensitized (thienycyclohexylpiperidine (TCP)) state, and this pharmacologically specific photolabeling was localized to the M2-9 leucine ring (δLeu(265), βLeu(257)) within the ion channel. In contrast, photolabeling within the αV8-20K was enhanced in the desensitized state and not inhibited by TCP but was inhibited by bupropion. This agonist-enhanced photolabeling was localized to αTyr(213) in αM1. These results establish the presence of two distinct bupropion binding sites within the Torpedo nAChR transmembrane domain: a high affinity site at the middle (M2-9) of the ion channel and a second site near the extracellular end of αM1 within a previously described halothane (general anesthetic) binding pocket.
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