Biosynthesis of pyrimidine nucleotides in mouse salivary glands stimulated with isoproterenol.

Cellular proliferation was stimulated with isoproterenol in submaxillary glands of mice. The activities ‘of both carbamyl-P synthetase and aspartate transcarbamylase were rapidly increased in response to isoproterenol, reaching a peak between 4 and 6 hours. The increase in activity of carbamyl-P synthetase was 2-fold, the increase in aspartate transcarbamylase was 1.5-fold. Incorporation of WO2 and [14C]orotate into RNA was also stimulated reaching a maximum within 2 hours. The bulk of [14C]orotate appeared in the RNA found in the nucleus. No [14C]orotate was incorporated into DNA, even if the glands were exposed to the [14C]orotate for 24 hours. The activity of uridine kinase was also stimulated by isoproterenol, although the maximum response was not obtained until 12 hours after injection. Incorporation of [Wluridine into RNA was stimulated within 8 hours of administration of isoproterenol, but there was no significant stimulation of the label into DNA. In contrast, labeled-thymidine was incorporated into DNA after a lag of 20 to 24 hours. The isoproterenol stimulated incorporation of orotate into RNA and thymidine into DNA was significantly inhibited by the administration of 6-azauridine, whereas incorporation of uridine into RNA was not inhibited.