Neurotropic action of MSH/ACTH 4-10 on neuromuscular function in hypophysectomized rats

These studies were designed to determine whether the previously demonstrated [24] enhancement of neuromuscular function by MSH/ACTH 4-10 is due to peptide action on the neurogenic and/or myogenic elements involved. The nerve muscle unit studied incorporated the sciatic nerve and its branches, and the extensors digitorum longus and brevis in the hypophysectomized rat, in situ. Parameters investigated included muscle action potentials (MAP) and muscle contractions (MC) during 30 min of stimulation (supramaximal, 10/sec; 0.05 msec duration). Resting membrane potentials and miniature endplate potential (mepp) characteristics were investigated in situ at neuromuscular junctions in the extensor digitorum brevis. Hypophysectomy results in markedly deleterious changes in neuromuscular function which can be partially alleviated by the administration of ACTH 4-10 (0.01 microgram/kg). This dosage increases MAP and MC amplitudes and reduces fatigue. Higher dosages (1.0 microgram/kg) have a depressing effect on these parameters. The facilitatory actions of ACTH 4-10 are abolished when the muscle is stimulated directly or stimulated through the peripheral stump of the cut nerve. ACTH 4-10 increases mepp frequency (a presynaptic event) but does not affect postsynaptic characteristics as measured by the resting membrane potential. These results indicate that MSH/ACTH 4-10 influences skeletal muscle function through a neurotropic action mediated by spinal motoneurons. Changes in the central excitatory state of higher motor centers are possibly involved.