Accession Number : ADA303734

Title :   Ethanol Disruption of Synaptic Neurotransmission.

Descriptive Note : Midterm rept. 22 Sep 94-21 Sep 95,

Corporate Author : DONALD GUTHRIE FOUNDATION FOR MEDICAL RESEARCH SAYRE PA

Personal Author(s) : Aronstam, Robert S.

PDF Url : ADA303734

Report Date : OCT 1995

Pagination or Media Count : 112

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.

Descriptors :   *NEUROTRANSMITTERS, *SYNAPSE, *CENTRAL NERVOUS SYSTEM, *ETHANOLS, *NERVE TRANSMISSION, *NEUROMUSCULAR TRANSMISSION, CONTROL, CALCIUM, TISSUES(BIOLOGY), BRAIN, QUANTITY, CELLS, MATERIALS, ADHESION, LIMITATIONS, RESPONSE, SIGNALS, LIGANDS, CLONES, HYPOTHESES, RECEPTION, SENSE ORGANS, PROTECTIVE TREATMENTS, MUSCARINE, NUCLEOTIDES, ADENYL CYCLASE, GUANINE, SYNAPSIS.

Subject Categories : Medicine and Medical Research
      Biochemistry
      Anatomy and Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE