Document Type
Article
Language
eng
Format of Original
9 p.
Publication Date
5-1995
Publisher
Society for Neuroscience
Source Publication
Journal of Neuroscience
Source ISSN
0270-6474
Abstract
Neuronal acetylcholine receptors, being highly permeable to calcium, are likely to regulate calcium-dependent events in neurons. Arachidonic acid is a membrane-permeant second messenger that can be released from membrane phospholipids by phospholipases in a calcium-dependent manner. We show here that activation of neuronal acetylcholine receptors triggers release of 3H-arachidonic acid in a calcium-dependent manner from neurons preloaded with the fatty acid. Moreover, low concentrations of arachidonic acid reversibly inhibit the receptors and act most efficiently on receptors likely to have the highest permeability to calcium, namely receptors containing α7 subunits. Low concentrations of arachidonic acid also reversibly inhibit α7- containing receptors expressed in Xenopus oocytes following injection of α7 cRNA. The oocyte results indicate following injection of α7 cRNA. The oocyte results indicate that the inhibition is a feature of the receptors rather than a consequence of neuron-specific machinery. The inhibition is not mediated by specific metabolites of arachidonic acid because the effects can be mimicked by other fatty acids; their effectiveness correlates with their content of double bonds. In contrast to arachidonic effects on calcium currents, inhibition of neuronal nicotinic receptors by the fatty acid cannot be prevented by blocking production of free radicals or by inhibiting protein kinase C. An alternative mechanism is that arachidonic acid binds directly to the receptors or perturbs the local environment in such a manner as to constrain receptor function.
Recommended Citation
Vijayaraghavan, Sukumar; Huang, Bo; Blumenthal, Edward M.; and Berg, Darwin K., "Arachidonic Acid as a Possible Negative Feedback Inhibitor of Nicotinic Acetylcholine Receptors on Neurons" (1995). Biological Sciences Faculty Research and Publications. 234.
https://epublications.marquette.edu/bio_fac/234
Comments
Published version. Journal of Neuroscience, Vol. 15, No. 5 (May 1995): 3679-3687. Permalink. © 1995 Society for Neuroscience. Used with permission.
Edward Blumenthal was affiliated with the University of California - San Diego at the time of publication.