DISTRIBUTION OF CALCITONIN-GENE-RELATED PEPTIDE IN VERTEBRATE NEUROMUSCULAR-JUNCTIONS - RELATIONSHIP TO THE ACETYLCHOLINE-RECEPTOR

Calcitonin gene-related peptide (CGRP), regarded by several authors to be involved in maintenance of the acetylcholine receptor, is present in the motor axons of various striated rat muscles. It is present, how ever, only in motor endplates of several selected striated muscles, wh ere it is located in presynaptic axon terminals of neuromuscular junct ions. No immunoreactivity could be seen within synaptic vesicles thems elves. In the non-human primate Macaca fasciculata, neuromuscular junc tions, including those in the diaphragm, display an intense CGRP react ion. The structure of the simian motor endplates is more elaborate tha n that of the rat. Amphibian motor nerve endings, both in tetanic and tonic muscles, display CGRP immunoreactivity. In tetanic muscles the C GRP reaction outlines ''terminaisons en placque'' (true motor end plat es) and weakly reacting ''terminaisons en grappe'' (grape-like endings ) in tonic muscles. On supramaximal stimulation of the motor nerve, CG RP is depleted from the affected neuromuscular junctions. Wallerian de generation of the motor axon results in complete disappearance of CGRP . In most rat muscles in which motor endplates do not normally exhibit CGRP immunoreactivity, e.g., the diaphragm and buccinator muscles, th e pre-terminal motor axons are CGRP-positive. After immobilization of such muscles by local bupivacaine injection to rats under brief chlora l hydrate anesthesia, CGRP immunoreactivity of the neuromuscular junct ions can be elicited because blockade of neuromuscular transmission re sults in accumulation of CGRP in the endplates. Even more striking is the appearance of CGRP immunoreactivity in normally non-reactive motor endplates during axon regeneration after an experimentally induced Wa llerian degeneration of the motor axons. We conclude that CGRP is a re gular, genotypically determined component of neuromuscular junctions, present either in a manifest or in a latent form. The latter can be el icited by various experimental approaches. The presence of CGRP in the motor endplate supports the theory that this peptide is instrumental in maintenance of the acetylcholine receptor.