Regulation of G protein-coupled muscarinic acetylcholine receptors (mAChRs) and delta-opioid receptors has been studied in neuroblastoma hybrids NCB-20 and NG108-15 cells. Exposure of NCB-20 cells to some mAChR agonists (carbachol, oxotremorine-M, and McN-A343) induce mAChR down-regulation, but other agonists such as pilocarpine and oxotremorine induce up-regulation, while another agonist, bethanecol, causes no change in the receptor number. These up- and down-regulations are blocked by atropine and involve corresponding changes in the density, but not affinity, of the receptor binding sites. A change in the m4-mAChR mRNA level is not involved in this modulation. In conjunction with Dr. Carmine Coscia's laboratory, adaptation of delta-opioid receptors has been studies in NG108-15 cells. Up-regulation of delta-receptors induced by two-day treatment with delta-receptor antagonists is preceded by a transient down-regulation of the receptor sites that occurs about 5 min after treatment. This down-regulation is accompanied by a decrease in the heavy membrane population of receptors and an increase in the binding sites in the light membrane fraction. Moreover, treatment with several delta-receptor antagonists induces a decrease in the specific activities of the lysosomal enzymes, suggesting that a retardation of receptor degradation is involved in the up-regulation. Novel nuclear delta- receptor binding sites are detected in intact purified nuclei and nuclear subfractions. Nuclear membranes contain newly synthesized G protein- coupled delta receptors, while chromatins contain internalized, uncoupled receptor binding sites. These nuclear delta-opioid receptors may partic- ipate in opioid functions that require gene transcription, such as opioid tolerance and dependence and modulation of brain development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002539-03
Application #
3781448
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code