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.

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.

Included in

Biology Commons

Share

COinS