Ethanol Disruption of Synaptic Neurotransmission.
Abstract
The goal of this research is to understand how acute and chronic ethanol administration disrupts synaptic transmission in the central nervous system. The underlying hypothesis is that ethanol depresses neurotransmission at neurotransmitter receptors by altering receptor- G protein interactions. The results provide partial support for our hypothesis. However, ethanol's actions were not universal, and receptor subtypes were not equally affected. The significance of ethanol's actions is indicated by the disruption of signaling processes (adenylate cyclase, intracellular Ca2+, cell adhesion). Ethanol disrupted the following processes: (1) receptor-G protein interactions as seen in ligand binding studies in receptors expressed by stably transfected CHO cells; (2) muscarinic receptor control of G protein GTPase activity and guanine nucleotide binding in brain tissues; (3) the balance between inhibitory and stimulatory G protein influences on adenylate cyclase, (4) Ca2+ responses of ml and m5 receptors; (5) muscarinic mediated cell adhesion response in a non-neuronal cell line. The quantity of experimental material has been a limiting factor in studies with cultured cells. We initiated studies on the influence of chronic ethanol treatment on neurotransmitter receptors, including the adoption of Western blots (G proteins) and Northern blots for receptor niRNA. To analyze control of receptor expression, the promoter regions of ml-m5 were cloned, sequenced and characterized.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1995
- Accession Number
- ADA303734
Entities
People
- Robert S. Aronstam