Calcitonin gene-related peptide (CGRP), a neuropeptide synthesized by motor neuron, is able to stimulate the expression of acetylcholine receptor (AChR) and acetylcholinesterase (AChE) that form the post-synaptic apparatus at the vertebrate neuromuscular junctions. Several lines of evidence indicate that the CGRP-induced AChE expression in muscle is mediated by the G-protein and acted through a cAMP-dependent pathway. First, various drugs affecting the intracellular level of cAMP could mimic the effect of CGRP in stimulating the expression of AChE in cultured myotubes. Second, when myotubes were transfected in vitro and in vivo with cDNA encoding the constitutively active mutant of G-protein a-subunit, the change in cAMP level paralleled with the change in the expression of AChE. Third,...[ Read more ]

Calcitonin gene-related peptide (CGRP), a neuropeptide synthesized by motor neuron, is able to stimulate the expression of acetylcholine receptor (AChR) and acetylcholinesterase (AChE) that form the post-synaptic apparatus at the vertebrate neuromuscular junctions. Several lines of evidence indicate that the CGRP-induced AChE expression in muscle is mediated by the G-protein and acted through a cAMP-dependent pathway. First, various drugs affecting the intracellular level of cAMP could mimic the effect of CGRP in stimulating the expression of AChE in cultured myotubes. Second, when myotubes were transfected in vitro and in vivo with cDNA encoding the constitutively active mutant of G-protein a-subunit, the change in cAMP level paralleled with the change in the expression of AChE. Third, the intracellular cAMP-dependent protein kinase (PKA) activity was increased by the application of CGRP. While the CGRP-induced AChE expression could be blocked by pre-incubating the myotubes with PKA inhibitors. Last, over- expression of the constitutively active transcription factors for ATF/CREB in cultured myotubes could stimulate the expression of AChE. Although the mRNA and protein levels of AChE were increased by CGRP, the enzymatic activity of the CGRP-induced AChE remained relatively unchanged. These findings indicate that the CGRP-induced AChE regulation is mediated by intracellular cAMP pathway, and represent the first evidence to suggest the mRNA synthesis of AChR and AChE could be mediated by a same neuron-derived factor.