Different Natures of Supersensitivity of Adenylate Cyclase Stimulated by Calcitonin Gene‐Related Peptide and Isoproterenol in Rat Diaphragm After Denervation and Reserpine Treatment

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Abstract
In skeletal muscles, calcitonin gene‐related peptide (CGRP) released from motor nerve terminals and humoral catecholamines stimulate adenylate cyclase (AC) and enhance muscle contraction. The effects of denervation and treatment with reserpine on twitch contraction and the AC system in rat diaphragm were investigated. The basal levels of twitch contraction and AC activity of the diaphragm of rats were both increased 2 weeks after phrenic nerve denervation but were not altered by treatment with reserpine. Reserpine treatment provoked supersensitivity of AC to isoproterenol, without affecting the response to CGRP. On the other hand, denervation decreased the activation of AC and enhancement of twitch contraction by CGRP, without affecting the responses to isoproterenol. These data suggest that denervation causes up‐regulation of AC as a result of loss of CGRP release from nerve terminal and that depletion of catecholamines by reserpine treatment supersensitizes the responses at the β‐adrenoceptor level. Thus, nervous and humoral factors regulate the AC system in striated muscle by different mechanisms.