The effect of isoproterenol and cycloheximide on protein synthesis and growth in mouse parotid

Abstract

Isoproterenol induces an increase in both cell size (hypertrophy) and cell number (hyperplasia) in the mouse parotid gland. The dose responses to isoproterenol of these two growth parameters are not identical because hypertrophy requires a severalfold lower dose. Cycloheximide injected 1 2 –1 hr after isoproterenol inhibits both growth responses but hyperplasia is more sensitive to this inhibitor. Isoproterenol depresses protein synthesis by about 50% during the first 6 hr after its administration, whereas cycloheximide (0.02–0.03 mg/g body wt) alone decreases protein synthesis by a similar amount but for much shorter periods. When cycloheximide is injected after isoproterenol the inhibition of protein synthesis is greater and the recovery does not follow the kinetics of cycloheximide-treated mice but parallels those of the isoproterenol-treated mice. Thus, isoproterenol appears to alter the organization and function of the acinar cells making the effects of cycloheximide more intense and prolonged than upon nonstimulated glands. Therefore, the effects of cycloheximide upon protein synthesis in the normal parotid cannot be extrapolated to glands that have been stimulated by isoproterenol. Mice treated with both cycloheximide and isoproterenol are completely refractory to the proliferative effects of a second isoproterenol injection for at least 4 hr and a full response is not restored until 14 hr later. This loss of response appears to be due to the initial isoproterenol administration rather than to the cycloheximide.