Protein kinase A regulates the degradation rate of Rs acetylcholine receptors.
Acetylcholine receptors at the neuromuscular junction of innervated vertebrate muscle (called Rs AChRs) have a stable degradation rate (t1/2 approximately 8-12 days) which accelerates after denervation to a half-life of approximately 3 days, but can be restabilized by reinnervation or by cAMP. We examined the mechanism by which cAMP regulates the Rs degradation rate. When dibutyryl cAMP (DB-cAMP) was applied to denervated mouse diaphragms in organ culture, it stabilized the accelerated degradation rate of the Rs. We found that this stabilization is reversible upon removal of the DB-cAMP, is cAMP specific and is mediated by intracellular cAMP. A major observation of this study is that the cAMP-induced stabilization of Rs AChRs is via protein kinase A (PKA), since H89, a PKA inhibitor, blocked the DB-cAMP induced stabilization of Rs, and H85, an analog of H89, which does not inhibit PKA but does inhibit other kinases as efficiently as H89, did not prevent the DB-cAMP-induced stabilization of Rs degradation. These results suggest that the cAMP messenger system via a PKA-dependent pathway could be among the mechanisms whereby the nerve regulates AChR degradation.
Xu
R
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Section of Neurobiology and Behavior, Cornell University, Ithaca, New York 14853-2702, USA.
Salpeter
M M
MM
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003964:Diaphragm / Q000378:metabolism / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009469:Neuromuscular Junction / Q000378:metabolism*; D009924:Organ Culture Techniques; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013449:Sulfonamides
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D011978:Receptors, Nicotinic; D013449:Sulfonamides; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide