Effects of Acetylcholinesterase Inhibition on Cholinergic Transmission in the Hippocampal Slice.
Abstract
This work is concerned with the mechanisms used by brain cells to change their functional inter-connections and the possibility that these are also involved in neuropathology. Three inter-related questions were studied: 1) what effects are produced in target neurons by prolonged exposure to neurotransmitters (e.g., acidic amino acids, acetylcholine); 2) does partial degradation of the submembrane cytoskeleton by calcium-activated proteases (calpain) affect synaptic organization; 3) are second messenger systems with known effects on growth (trophic) responses in peripheral tissues activated by intense physiological events in brain. Prolonged exposure of brain slices to acidic amino acid transmitters causes functional desensitization of extra-synaptic receptors, and a very potent inhibition of the second messenger system normally activated by cholinergic receptor. 2) Experiments concerned with synaptic structural proteins (brain spectrin or fodrin) and a proteolytic enzyme (calpain) that digests them produced the following results: a) degradation of spectrin by calpain changes irreversibly amino acid receptors; b) calpain is concentrated in synaptic regions; c) calpain-spectrin interactions in a test system (red blood cells) result in pronounced morphological changes; d) spectrin is rapidly synthesized, inserted into membrane domains, and apparently digested by calpain; e) the calpain-fodrin interaction is accelerated by calmodulin.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 02, 1986
- Accession Number
- ADA169047
Entities
People
- Gary Lynch
Organizations
- University of California, Irvine