Release of calcitonin gene-related peptide-like immunoreactive substance from neuromuscular junction by nerve excitation and its action on striated muscle.

In a rat phrenic nerve-hemidiaphragm preparation, calcitonin gene-related peptide (CGRP) increased the twitch contraction induced by nerve or transmural stimulation dose dependently. Either electrical or high K+ stimulation of the phrenic nerve caused release of a CGRP-like immunoreactive substance (CGRP-LIS) in a Ca2(+)-dependent manner. Electrical stimulation of the phrenic nerve also increased the cyclic AMP content in diaphragm. This increase was not observed in Ca2(+)-free medium and was blocked by antiserum against CGRP. These results indicate that excitation of the motor nerve causes release of CGRP-LIS at nerve terminals and that the released CGRP-LIS increases the cyclic AMP content of skeletal muscles and potentiates twitch contraction.