Calcitonin gene-related peptide: possible role in formation and maintenance of neuromuscular junctions.

The expression and content of calcitonin gene-related peptide (CGRP) and secretogranin II (SgII) in adult rat motor neurons were examined by in situ hybridization, Northern blot analysis, and immunocytochemistry. Normal motor nerve terminals did not contain detectable CGRP or SgII. Ten to 15 days after a peripheral nerve crush about 80% of the motor nerve terminals reinnervating the soleus (SOL) muscle contained detectable CGRP but no SgII. Thereafter, the percentage of CGRP-positive terminals declined towards zero. In the spinal cord, CGRP expression was higher than normal 1 d after a sciatic nerve crush and increased during the next few days. No increase in SgII expression was observed. Nerve blocks by tetrodotoxin (TTX) and botulinum toxin (BoTX) increased CGRP content and expression in motor neurons but had no effect on SgII. After 10 d of BoTX treatment and 33 d of TTX treatment (the longest time points studied), more than 90% of the motor nerve terminals stained for CGRP. The density of large dense core vesicles (LDCVs) was also higher than normal in such terminals. Some increase in CGRP content and expression occurred in the nontreated side. In a group of rats, the peroneal nerve was stimulated electrically with brief, intermittent pulse trains at 100 Hz. The stimulation was applied below a TTX block that had started 7 or 19 d earlier. One minute of such stimulation was sufficient to remove CGRP from most of the terminals.(ABSTRACT TRUNCATED AT 250 WORDS)