Age-dependent regulation of isoproterenol-stimulated DNA synthesis in rat salivary gland in vivo

Abstract

In an attempt to determine the initial isoproterenol-stimulated response on which the age-dependent delay in DNA synthesis is based, the time course and magnitude of several previously documented biochemical events within this sequence were examined. An increase in activity of thymidine kinase, and perhaps deoxythymidylate synthesis, is initiated at 12 hr following treatment with isoproterenol, and is delayed nearly 5 hr as rats age from 2 to 12 months. Incorporation of [ 3H]-uridine into total cellular RNA following isoproterenol injection is initiated at 7 hr in 2-month old rats and occurs as early as 2 hr in 12-month old rats. However, this age-dependent acceleration of apparent RNA synthesis probably is not essential to subsequent synthesis of DNA. The appearance of RNA species required for DNA synthesis, as determined by the time of insensitivity to inhibition by Actinomycin D, occurs at 10 hr following isoproterenol treatment of 2-month old rats, and is delayed nearly 12 hr in 12-month old rats. The possible appearance of protein species required for DNA synthesis, as determined by the time of diminished sensitivity to inhibition by cycloheximide, occurs at 5 hr following isoproterenol treatment of both 2- and 12-month old rats. It is proposed that the initial age dependent modification relates to either the stimulated appearance of crucial RNA species between 5 and 10 hr following isoproterenol treatment, or an early biochemical action of the drug, distinct from its membrane receptor binding which enhances secretion of α-amylase.