Protein Synthesis in the Early Prereplicative Phase of Isoproterenol-stimulated Synthesis of Deoxyribonucleic Acid

Abstract The stimulation of DNA synthesis which occurs in mouse salivary gland 20 to 30 hours after a single administration of isoproterenol is inhibited by drugs that inhibit protein synthesis. Both cycloheximide and puromycin are most effective in inhibiting isoproterenol-stimulated DNA synthesis when given 1 hour after the isoproterenol. At this time, the aminonucleoside of puromycin has no effect on the subsequent onset of DNA synthesis. Although cycloheximide has only a temporary effect on protein synthesis in mouse salivary gland, its effect on isoproterenol-stimulated DNA synthesis, when given 1 hour after isoproterenol, consists not in a mere delay but in a true inhibition. The free ribosome fraction of mouse salivary gland shows an increase in protein synthesis 1 hour after isoproterenol, when the stimulated gland is incubated in vitro. In addition, ribosomes isolated from salivary glands of mice killed 1 hour after the administration of isoproterenol have a higher amino acid-incorporating activity in a cell-free system than free ribosomes isolated from control salivary glands. This increased capacity for protein synthesis is accompanied by an increase in the number of free polysomes in the stimulated gland. These results indicate that isoproterenol causes an early stimulation of protein synthesis in mouse salivary gland and that this stimulation is relevant to the subsequent onset of DNA synthesis.