Abstract
Correlation between denervation-induced ACh supersensitivity and protein synthesis was studied at cellular and tissue levels in tissues from rat diaphragms. Effects of unilateral denervation of diaphragm muscles on the incorporation of 14C-L-leucine into the total proteins were tested. After denervation, there were increases of 4.5 times within 2 days and double the increase was seen in 14 days in the rate of incorporation of 14C-L-leucine into the paralyzed hemidiaphragm. The administration of cycloheximide (1.0 mg/kg i.v.), in amounts that had experimentally hardly any effect on the incorporation into the normal muscle, suppressed their increases into the denervated muscles. From the rates of 3H-puromycin incorporation into the nascent proteins of microsomal fractions from both normal and denervated diaphragms, the reactivities of diaphragm microsomal fractions with puromycin were shown to be enhanced by denervation. In experiments on isolated muscle suspended in a bath containing modified Tyrode solution, the inhibitory effects of cycloheximide (CHI) on ACh submaximal contractions induced by supersensitivities after 5 days' denervation were depressed to a greater extent than were those after 2 weeks' denervation followed by injection of 1.0 mg/kg CHI into rat at one hour before removal of the diaphragm. These results indicate that denervation induces an increase in the rate of protein synthesis and that ACh supersensitivity is closely related to the enhanced rate of protein synthesis.
