Isoproterenol-induced Phase Shifts in Circadian Rhythm of Mitosis in Murine Corneal Epithelium

The stimulation of DNA synthesis and subsequent mitosis by isoproterenol (IPR) was thought to occur only in the parotid gland and kidney (I, 2). In the parotid gland, the peak in DNA synthesis occurred 28 h after a single injection of IPR. It recently was demonstrated in mice that the duodenum also responds to a single "aperitoneal iniection of IPR (3). The total ake of [~H]thymidine ([~H]Tdr) into all three ,~f the above-mentioned organs fluctuated with a circadian frequency in both salineand IPRtreated animals. In the duodenum the amount of [3H]Tdr uptake in the IPR-treated animals was dependent on the phase of the mouse circadian system at which the IPR was injected: during one phase it increased, at another it decreased and at still another phase, no statistically significant effect on total [3H]Tdr uptake was noted. Recently it was reported that a single injection of IPR resulted in an "inhibi t ion" of mitosis 24 h after injection and a "st imulation" at 48 h in rat lens epithelium (4, 5). The present report demonstrates that the results obtained from a single injection of I P R can be misleading without time series analysis. I P R changes the phasing and thus alters the profile of the normal circadian rhythm.