Inhibition of calcium channels by opioid- and adenosine-receptor agonists in neurons of the nucleus accumbens
Description
1. The pharmacological effects of opioid- and adenosine-receptor agonists on neural signalling were investigated by measuring drug actions on barium current flowing through calcium channels in acutely-dissociated neurons of the rat nucleus accumbens (NAc). 2. Under whole-cell voltage clamp, opioids acted via μ, but not δ or κ, receptors to partially inhibit barium current. Mean inhibition was 35±2% (± s.e.mean, n= 33) for methionine-enkephalin and 37 ± 1% (n = 65) for the selective μ receptor...[Show more]
dc.contributor.author | Chieng, Billy | |
---|---|---|
dc.contributor.author | Bekkers, John | |
dc.date.accessioned | 2015-12-10T22:41:31Z | |
dc.identifier.issn | 0007-1188 | |
dc.identifier.uri | http://hdl.handle.net/1885/57959 | |
dc.description.abstract | 1. The pharmacological effects of opioid- and adenosine-receptor agonists on neural signalling were investigated by measuring drug actions on barium current flowing through calcium channels in acutely-dissociated neurons of the rat nucleus accumbens (NAc). 2. Under whole-cell voltage clamp, opioids acted via μ, but not δ or κ, receptors to partially inhibit barium current. Mean inhibition was 35±2% (± s.e.mean, n= 33) for methionine-enkephalin and 37 ± 1% (n = 65) for the selective μ receptor agonist DAMGO, both measured at saturating agonist concentrations in neurons with diameter ≥ 20 μm. EC50 for DAMGO was 100 nM. Perfusion of naloxone reversed the current inhibition by DAMGO. 3. Adenosine also partially inhibited barium current in these neurons. Mean inhibition was 28 ± 2% (n=29) for adenosine and 33±3% (n=27) for the selective A1 receptor agonist N6CPA, both at saturating concentrations in neurons with diameter ≥20 μm. EC50 for N6CPA was 34 nM. Adenosine inhibition was reversed by perfusion of an A1 receptor antagonist, 8-cyclopentyl-l,3-dipropylxanthine, while the selective A2A receptor agonist, CGS 21680, had no effect. 4. Inhibition by opioids and adenosine was mutually occlusive, suggesting a converging pathway onto calcium channels. 5. These actions involved a G-protein-coupled mechanism, as demonstrated by the partial relief of inhibition by strong depolarization and by the application of N-ethylmaleimide or GTP-γ-S. 6. Inhibition of barium current by opioids had their greatest effect in large neurons, that is, in presumed interneurons. In contrast, opioid inhibition in neurons with diameter ≤15 μm was 11±2% (n=26) for methionine-enkephalin and 11±4% (n= 17) for DAMGO, both measured at saturating agonist concentrations. Adenosine inhibition in neurons with diameter ≤ 15 μm was 22±5% (n = 9). 7. These results implicate the interneurons as a locus for the modulation of the excitability of projection neurons in the NAc during the processes of addiction and withdrawal. | |
dc.publisher | Nature Publishing Group | |
dc.source | British Journal of Pharmacology | |
dc.subject | Keywords: 2 [4 (2 carboxyethyl)phenethylamino]adenosine 5' (n ethylcarboxamide); 6 n cyclopentyladenosine; 8 cyclopentyl 1,3 dipropylxanthine; adenosine; adenosine A1 receptor agonist; adenosine A1 receptor antagonist; adenosine A2a receptor agonist; barium ion; ca Adenosine; Calcium channel; DAMGO; Interneuron; Nucleus accumbens; Opioid; Opioid withdrawal | |
dc.title | Inhibition of calcium channels by opioid- and adenosine-receptor agonists in neurons of the nucleus accumbens | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.description.refereed | Yes | |
local.identifier.citationvolume | 133 | |
dc.date.issued | 2001 | |
local.identifier.absfor | 110902 - Cellular Nervous System | |
local.identifier.ariespublication | MigratedxPub422 | |
local.type.status | Published Version | |
local.contributor.affiliation | Chieng, Billy, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Bekkers, John, College of Medicine, Biology and Environment, ANU | |
local.description.embargo | 2037-12-31 | |
local.bibliographicCitation.startpage | 337 | |
local.bibliographicCitation.lastpage | 344 | |
dc.date.updated | 2015-12-09T11:08:43Z | |
local.identifier.scopusID | 2-s2.0-0034763925 | |
Collections | ANU Research Publications |
Download
File | Description | Size | Format | Image |
---|---|---|---|---|
01_Chieng_Inhibition_of_calcium_channels_2001.pdf | 202.78 kB | Adobe PDF | Request a copy |
Items in Open Research are protected by copyright, with all rights reserved, unless otherwise indicated.
Updated: 17 November 2022/ Responsible Officer: University Librarian/ Page Contact: Library Systems & Web Coordinator