Modulation of protein synthesis in a cell-free system derived from rat brain by corticotropin (ACTH), magnesium, and spermine.

Modulation of protein synthesis by fragments of the ACTH molecule has been studied in a cell-free system obtained from subcortical brain tissue of rats. Both the activity of the protein-synthesizing system and its sensitivity to ACTH-like peptides appeared to be highly dependent on the Mg2+ and spermine concentrations. At optimal Mg2+ concentrations (4 mM) the peptide sequences ACTH(1-24) and (11-24) were both inhibitory, the latter being the more active. The inhibitory effect was reduced or abolished at higher (suboptimal) concMg2+ concentrations. Spermine, like ACTH, inhibited protein synthesis at the optimal Mg2+ concentration. However, at lower Mg2+ concentrations spermine had a stimulatory effect and maximal activity was obtained at 0.75-1.0 mM Mg2+. In the presence of spermine (60 microM) and Mg2+ (0.75 mM), a half-maximal inhibition of protein synthesis was obtained with a peptide concentration of 5 microM. A structure-activity study showed that the peptides ACTH(7-16)-NH2, (11-24), (5-18, 17Lys 18Lys)-NH2 and (15-24) were active in inhibiting protein synthesis, whereas the fragments ACTH(1-16)-NH2 and (17-24) were inactive. The results are discussed in terms of an interaction between ACTH, Mg2+, and spermine, and intracellular processes involved in protein synthesis.