2003
DOI: 10.1021/bi034052n
|View full text |Cite
|
Sign up to set email alerts
|

Noncompetitive Antagonist Binding Sites in the Torpedo Nicotinic Acetylcholine Receptor Ion Channel. Structure−Activity Relationship Studies Using Adamantane Derivatives

Abstract: We used a series of adamantane derivatives to probe the structure of the phencyclidine locus in either the resting or desensitized state of the nicotinic acetylcholine receptor (AChR). Competitive radioligand binding and photolabeling experiments using well-characterized noncompetitive antagonists such as the phencyclidine analogue [piperidyl-3,4-(3)H(N)]-N-[1-(2-thienyl)cyclohexyl]-3,4-piperidine ([(3)H]TCP), [(3)H]ethidium, [(3)H]tetracaine, [(14)C]amobarbital, and 3-(trifluoromethyl)-3-(m-[(125)I]iodophenyl… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
2
1

Citation Types

6
63
0

Year Published

2004
2004
2023
2023

Publication Types

Select...
7

Relationship

2
5

Authors

Journals

citations
Cited by 36 publications
(69 citation statements)
references
References 34 publications
6
63
0
Order By: Relevance
“…To determine receptor selectivity, the effect of varenicline on [ 3 H] MLA (4.1 nM) binding to hα7 nAChRs, on [ 3 H]epibatidine (4.6 nM) binding to hα3β4 nAChRs, and on [ 3 H]cytisine (9.1 nM) binding to hα4β2, hα4β4, and Torpedo nAChRs, respectively, was studied as previously described [19][20][21][22]. To determine whether varenicline interacts with the Torpedo and hα4β2 nAChR ion channels, additional studies were conducted using [ 3 H]TCP (20 nM) [21] and [ 3 H]imipramine (13 nM) [23].…”
Section: Radioligand Competition Binding Experimentsmentioning
confidence: 99%
See 1 more Smart Citation
“…To determine receptor selectivity, the effect of varenicline on [ 3 H] MLA (4.1 nM) binding to hα7 nAChRs, on [ 3 H]epibatidine (4.6 nM) binding to hα3β4 nAChRs, and on [ 3 H]cytisine (9.1 nM) binding to hα4β2, hα4β4, and Torpedo nAChRs, respectively, was studied as previously described [19][20][21][22]. To determine whether varenicline interacts with the Torpedo and hα4β2 nAChR ion channels, additional studies were conducted using [ 3 H]TCP (20 nM) [21] and [ 3 H]imipramine (13 nM) [23].…”
Section: Radioligand Competition Binding Experimentsmentioning
confidence: 99%
“…To determine whether varenicline interacts with the Torpedo and hα4β2 nAChR ion channels, additional studies were conducted using [ 3 H]TCP (20 nM) [21] and [ 3 H]imipramine (13 nM) [23]. The effect of varenicline on [ 3 H]cytisine, in the absence (nAChRs are in the resting but activatable state) and presence of 200 μM proadifen [24], and [ 3 H]TCP binding, in the presence of 1 mM CCh (nAChRs are mainly in the desensitized state), was also determined as previously described [21,23] After incubation (2 h), nAChR-bound radioligand was separated from free radioligand by a filtration assay [19][20][21][22][23]. The concentrationresponse data were curve-fitted by nonlinear least squares analysis using the Prism software (GraphPad Software, San Diego, CA).…”
Section: Radioligand Competition Binding Experimentsmentioning
confidence: 99%
“…However, there is much evidence that the ion pore admits large molecules only from the extracellular side and that depth of penetration into the pore is a function of molecular size [2,3,6,[29][30][31][32][33][34]. As a result, it seems clear that the pore must be shaped like a funnel that opens toward the extracellular side (Fig.…”
Section: Finding a Template For The Pentameric Ion Porementioning
confidence: 99%
“…This structure has been suggested to be a progenitor of pentameric ion channels [30]. We previously used the five pore-lining alpha helices in this structure as a template for aligning the pore-lining transmembrane segment 2 (TM2) in models of GABAAR, GlyR, and nAChR ion channels [1,[6][7][8]18,32]. The MscL structure also contains five outer alpha helices that contribute to the ion channel only as the funnel-shaped pore widens outward on the extracellular side.…”
Section: Finding a Template For The Pentameric Ion Porementioning
confidence: 99%
“…To characterize mTFD-MPAB interactions with the transmitter binding sites, we compared its effects on the equilibrium binding of [ H]TCP, a PCP analog; Katz et al, 1997;Arias et al, 2003Arias et al, , 2006. Binding assays were performed in the presence of Carb, an agonist that stabilizes nAChRs in the desensitized state, or a-BgTx, a competitive antagonist that stabilizes the nAChR in the resting state.…”
Section: Photoaffinity Labeling Nachr Barbiturate Binding Sitesmentioning
confidence: 99%