Neuroscience 2005 Abstract
| Presentation Number: | 952.7 |
|---|---|
| Abstract Title: | Hydroxyindole enhancement of benzylidene-anabaseine binding to rat brain α7 nicotinic acetylcholine receptors. |
| Authors: |
MacDougall, K. N.*1
; Wildeboer, K. M.1
; Soti, F.1
; Kem, W. R.1
1Dept. Pharmacology and Therapeutics, Univ. of Florida Col. of Medicine, Gainesville, FL |
| Primary Theme and Topics |
Neural Excitability, Synapses, and Glia: Cellular Mechanisms - Ligand-Gated Ion Channels -- Nicotinic acelylcholine receptors: Physiology |
| Secondary Theme and Topics | Disorders of the Nervous System<br />- Addiction and Drugs of Abuse<br />-- Nicotine |
| Session: |
952. Nicotinic Acetylcholine Receptors: Physiology II Poster |
| Presentation Time: | Wednesday, November 16, 2005 3:00 PM-4:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # D63 |
| Keywords: | Nicotinic Receptor, Nicotine, Acetylcholine, Drug |
5HI (5-hydroxyindole) enhances the affinity of α7 nAChR agonists but not antagonists for this receptor (Grantham et al., 2004, SFN Mtg Abstr. 956.13). In principle, this radioligand binding assay could be used to rapidly identify agonists within a large library of compounds. We measured 5HI enhancement of the binding affinities of several benzylidene-anabaseines whose apparent efficacies had been measured by electrophysiological methods (Papke et al., 2004; Stokes et al., 2004). Anabaseine (>95% ACh current) was a full agonist, 3-(2,4-Dihydroxybenzylidene)-anabaseine (67% ACh) and (3-(2,4-Dimethoxybenzylidene)-anabaseine, DMXBA) (47% ACh) were strong partial agonists, and 3-(4-Thiomethoxybenzylidene)-anabaseine (15% ACh) was a very weak partial agonist. The ability of each compound to displace 125I-BTX binding was determined in the presence or absence of 2 mM 5HI. At least 10 different agonist concentrations in quadruplicate were used to generate each Prism software-fitted curve. Enhancement of unlabelled agonist binding was estimated as the ratio of the calculated IC50 in the absence of 5HI / IC50 in the presence of 5HI. The 5HI did not affect specific or non-specific BTX binding in the absence of a competing ligand. The measured 5HI enhancements (4- to 7-fold) of agonist binding were not very different, in spite of large differences in their apparent efficacies. Thus, the electrophysiologically measured apparent efficacies of the benzylidene-anabaseines may be affected by other factors in addition to the open state probability of the agonist-occupied receptor. (Supported by NIH RO1 MR6142).
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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