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 t he 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 nerv e motor neurons which supply the gracilis muscle, as well as in the corresp onding motor endplate regions where high levels of both AChE activity and a cetylcholine receptors (AChRs) are detected; (b) endplate-associated CGRP d eclines with muscle denervation several hours before any changes in AChE fo rms are detected; (c) a single subcutaneous injection of CGRP reversibly re duces the activities of all AChE forms in endplate regions of normally inne rvated and otherwise untreated gracilis muscles; and (d) similar treatment with hCGRP(8-37), a potent and selective CGRP antagonist, produces the oppo site 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 m uscles. Indeed, the findings lend strong support to the hypothesis that ner ve-derived CGRP plays a key role in the trophic regulation of AChE forms at the neuromuscular junction. (C) 1999 Published by Elsevier Science B.V. Al l rights reserved.