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Mode of cembranoid action on embryonic muscle acetylcholine receptor.
- Source :
-
Journal of neuroscience research [J Neurosci Res] 2008 Jan; Vol. 86 (1), pp. 93-107. - Publication Year :
- 2008
-
Abstract
- The mechanism of eupalmerin acetate (EUAC) actions on the embryonic muscle nicotinic acetylcholine receptor (nAChR) in BC3H-1 cells was studied by using whole-cell and single-channel patch-clamp current measurements. With whole-cell currents, EUAC did not act as an agonist on this receptor. Coapplication of 30 microM EUAC with 50 microM, 100 microM, or 500 microM carbamoylcholine (CCh) reversibly inhibited the current amplitude, whereas, with 20 microM CCh, current was increased above control values in the presence of EUAC. EUAC concentration curves (0.01-40 microM) obtained with 100 microM and 500 microM CCh displayed slope coefficients, n(H), significantly smaller than one, suggesting that EUAC bound to several sites with widely differing affinities on the receptor molecule. The apparent rate of receptor desensitization in the presence of EUAC and CCh was either slower than or equal to that obtained with CCh alone. The major finding from single-channel studies was that EUAC did not affect single-channel conductance or the ability of CCh to interact with the receptor. Instead, EUAC acted by increasing the channel closing rate constant. The results are not consistent with the competitive model for EUAC inhibition, with the sequential open-channel block model, or with inhibition by increased desensitization. The data are best accounted for by a model in which EUAC acts by closed-channel block at low concentrations, by positive modulation at intermediate concentrations, and by negative allosteric modulation of the open channel at high concentrations.
- Subjects :
- Animals
Cell Line, Transformed
Diterpenes chemistry
Diterpenes pharmacology
Dose-Response Relationship, Drug
Dose-Response Relationship, Radiation
Drug Interactions
Electric Stimulation
Ion Channel Gating physiology
Membrane Potentials drug effects
Membrane Potentials physiology
Membrane Potentials radiation effects
Mice
Myoblasts physiology
Myoblasts radiation effects
Patch-Clamp Techniques methods
Carbachol pharmacology
Cholinergic Agonists pharmacology
Ion Channel Gating drug effects
Myoblasts drug effects
Receptors, Nicotinic physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0360-4012
- Volume :
- 86
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of neuroscience research
- Publication Type :
- Academic Journal
- Accession number :
- 17868151
- Full Text :
- https://doi.org/10.1002/jnr.21468