TY - JOUR
T1 - Cyclic AMP stabilizes the degradation of original junctional acetylcholine receptors in denervated muscle
AU - Shyng, S. L.
AU - Xu, R.
AU - Salpeter, M. M.
N1 - Funding Information:
We thank Daniel Wetzel, Dorothy Bell, and Iris Greenberg for assistance with these experiments, Tom Podleski and Ron Harris-Warrick for helpful discussion, and Deborah Moslehi for preparing the manuscript. This work was supported by grants from the National Institutes of Health (NS09315) and from the Cornell University Biotechnology Program sponsored by the N.Y. State Science and Technology Foundation, by a consortium of industries, and by the United States Army Research Office and NSF.
PY - 1991/3
Y1 - 1991/3
N2 - We used mouse diaphragm muscle in organ culture to study the stabilization of acetylcholine receptor (AChR) degradation at denervated neuromuscular junctions. After denervation, the degradation rate of the AChRs present prior to denervation (slowly degrading, or Rs, AChRs) accelerates from the predenervation degradation half-life (t 1 2) of ∼8-10 days to a t 1 2 of ∼2-3 days. We report that addition to the organ culture medium of pharmacological agents that elevate cytoplasmic cAMP levels (forskolin, dibutyryl cAMP, and 8-bromo-cAMP) reversed the change in 42 caused by denervation, whereas addition of 1,9-dideoxyforskolin, a forskolin analog that does not elevate cytoplasmic cAMP levels, did not reverse the effect of denervation. The degradation rate of AChRs in primary myotube cultures and that of the newly synthesized AChRs in denervated muscle were little affected by forskolin or dibutyryl cAMP. The possibility is raised that the modulation of Its AChR degradation by innervation may be mediated by CAMP.
AB - We used mouse diaphragm muscle in organ culture to study the stabilization of acetylcholine receptor (AChR) degradation at denervated neuromuscular junctions. After denervation, the degradation rate of the AChRs present prior to denervation (slowly degrading, or Rs, AChRs) accelerates from the predenervation degradation half-life (t 1 2) of ∼8-10 days to a t 1 2 of ∼2-3 days. We report that addition to the organ culture medium of pharmacological agents that elevate cytoplasmic cAMP levels (forskolin, dibutyryl cAMP, and 8-bromo-cAMP) reversed the change in 42 caused by denervation, whereas addition of 1,9-dideoxyforskolin, a forskolin analog that does not elevate cytoplasmic cAMP levels, did not reverse the effect of denervation. The degradation rate of AChRs in primary myotube cultures and that of the newly synthesized AChRs in denervated muscle were little affected by forskolin or dibutyryl cAMP. The possibility is raised that the modulation of Its AChR degradation by innervation may be mediated by CAMP.
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U2 - 10.1016/0896-6273(91)90254-W
DO - 10.1016/0896-6273(91)90254-W
M3 - Article
C2 - 1848083
AN - SCOPUS:0026131492
SN - 0896-6273
VL - 6
SP - 469
EP - 475
JO - Neuron
JF - Neuron
IS - 3
ER -