The cAMP-dependent protein kinase mediates the expression of AChE in chick myotubes

Calcitonin gene-related peptide (CGRP), a neuropeptide synthesized by motor neurons, stimulates the expression of AChR and AChE at the vertebrate neuromuscular junctions. The signaling mechanism of CGRP-induced AChE expression in muscle was determined both in vitro and in vivo. In cultured chick myotubes, the intracellular cAMP-dependent protein kinase (PKA) activity increased to similar to 2-fold after the application of CGRP or PKA activators; the induction was blocked by PKA inhibitors, in vivo transfection analysis on chick gastrocnemius muscles showed that the transfection of cDNA encoding constitutively active mutant G alpha(s) increased the expression of AChE mRNA and protein to similar to 2-fold, while the constitutively active mutant G alpha(i) cDNA transfection showed an opposite effect. The induced catalytic subunit of AChE at similar to 105 kDa was determined by specific antibody. These findings indicate that the CGRP-induced AChE expression in chick muscle is mediated by a PKA-dependent pathway. NeuroReport 11:801-806 (C) 2000 Lippincott Williams & Wilkins.