Accession Number : ADB136473

Title :   Turnover of Acetylcholine Receptors: Mechanisms of Regulation.

Descriptive Note : Annual rept. 1 Aug 85-31 Jul 86,

Corporate Author : JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE

Personal Author(s) : Drachman, Daniel B. ; Pestronk, Alan ; Ramsay, David A. ; Lipsky, Naomi ; Avila, Orlando

Report Date : 01 AUG 1986

Pagination or Media Count : 38

Abstract : The synthesis, insertion and degradation of acetylcholine receptors (AChRs) of skeletal muscle cells is closely regulated both by the muscle cells and by the motor nerves that supply them. The goal of this project is to elucidate the mechanisms of regulation of the AChRs, both at the neuromuscular junction and at extrajunctional regions. We have used Iodine 125-alpha-bungarotoxon (alpha-BuTx) as a label to follow the metabolic turnover of AChRs both in vivo and in tissue culture. Recent experiments have used cDNA that specifically binds to the mRNA for the alpha-subunit of the AChR to measure transcription of the gene, as well. To date, our experiments have shown: That AChRs at normally innervated rodent neuromuscular junctions turn over at two different rates; The rapidly turning over AChRs (RTOs) are synthesized and inserted into the junction at an extremely rapid rate, sufficient to maintain a steady state; This rapid rate of resynthesis can account for the rapid recovery of neuromuscular junctions after blockade with irreversible blocking agents such as alpha-BuTx; A proportion of the RTOs serve as precursors for the stable AChRs; Synthesis of extrajunctional AChRs in cultured skeletal muscle can be down-regulated by the cations lithium, calcium, and sodium; Denervation results in a marked increase in expression of the gene for the alpha-subunit for AChR, in skeletal muscle. (kt)

Descriptors :   *ACETYLCHOLINE, NERVE CELLS, NERVE BLOCKING, MUSCULOSKELETAL SYSTEM, CALCIUM, CATIONS, CELLS, DEGRADATION, NEUROCHEMISTRY, NERVE TRANSMISSION, GENES, HIGH RATE, IN VIVO ANALYSIS, IRREVERSIBLE PROCESSES, JUNCTIONS, LITHIUM, MOTORS, MUSCLES, NERVES, RECOVERY, REGULATIONS, RODENTS, SENSES(PHYSIOLOGY), SODIUM, STEADY STATE, SYNTHESIS, TISSUE CULTURE.

Subject Categories : Anatomy and Physiology
      Toxicology

Distribution Statement : APPROVED FOR PUBLIC RELEASE