Cyclic AMP stabilizes the degradation of original junctional acetylcholine receptors in denervated muscle.
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 (t1/2) of approximately 8-10 days to a t1/2 of approximately 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 t1/2 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 Rs AChR degradation by innervation may be mediated by cAMP.
Shyng
S L
SL
Section of Neurobiology and Behavior, Cornell University, Ithaca, New York 14853-2702.
Xu
R
R
Salpeter
M M
MM
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D003964:Diaphragm; D005260:Female; D007365:Intercellular Junctions / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D051379:Mice; D009121:Muscle Denervation; D009132:Muscles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009924:Organ Culture Techniques; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000502:physiology
D011950:Receptors, Cholinergic; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D000242:Cyclic AMP