Neurogenic calcitonin gene-related peptide: a neurotrophic factor in the maintenance of acetylcholinesterase molecular forms in adult skeletal muscles.

This work addresses the role of calcitonin gene-related peptide (CGRP) in the physiological maintenance of acetylcholinesterase (AChE) molecular forms in motor endplate regions of adult Sprague-Dawley rat fast-twitch anterior gracilis muscles. Results show that: (a) CGRP is present in obturator nerve motor neurons which supply the gracilis muscle, as well as in the corresponding motor endplate regions where high levels of both AChE activity and acetylcholine receptors (AChRs) are detected; (b) endplate-associated CGRP declines with muscle denervation several hours before any changes in AChE forms are detected; (c) a single subcutaneous injection of CGRP reversibly reduces the activities of all AChE forms in endplate regions of normally innervated and otherwise untreated gracilis muscles; and (d) similar treatment with hCGRP(8-37), a potent and selective CGRP antagonist, produces the opposite effects, i.e., it reversibly elevates the activities of all AChE forms. These and other findings indicate that CGRP and hCGRP(8-37) influence the mechanism(s) by which AChE forms are maintained in intact adult gracilis muscles. Indeed, the findings lend strong support to the hypothesis that nerve-derived CGRP plays a key role in the trophic regulation of AChE forms at the neuromuscular junction.