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.
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002474:Cell-Free System; D007930:Leucine / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013096:Spermine / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D009419:Nerve Tissue Proteins; D013096:Spermine; D000324:Adrenocorticotropic Hormone; D007930:Leucine; D008274:Magnesium