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BETA ADRENERGIC CONTROL OF MACROMOLECULE SYNTHESIS IN NEONATAL RAT HEART, KIDNEY AND LUNG: RELATIONSHIP TO SYMPATHETIC NEURONAL DEVELOPMENT
Citation:
Slotkin, T., W. Whitmore, L. Orband-Miller, K. Queen, AND K. Haim. BETA ADRENERGIC CONTROL OF MACROMOLECULE SYNTHESIS IN NEONATAL RAT HEART, KIDNEY AND LUNG: RELATIONSHIP TO SYMPATHETIC NEURONAL DEVELOPMENT. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-87/517.
Description:
The sympathetic nervous system has been hypothesized to coordinate the timing of cellular development in peripheral tissues. n the current study, we evaluated the relationships among the ontogeny of sympathetic projections to peripheral organs, the patterns of macromolecule synthesis in those organs and the reactivity of synthetic processes to beta adrenergic stimulation by isoproterenol. he major developmental rise in norepinephrine concentration and turnover, as well as in numbers of beta receptors, occurred during the second to fourth postnatal weeks in renal and lung sympathetic pathways and slightly earlier in the cardiac-sympathetic axis. he developmental decline in DNA synthesis in heart, kidney and lung coincided with the maturation of sympathetic projections. irect stimulation of beta receptors by the in vivo administration of isoproterenol caused acute reductions in DNA synthesis in an age-dependent manner. n the heart, isoproterenol was first able to suppress DNA synthesis at 5 days of age and a maximal effect was seen at 9 days; this early phase was characterized by a rapid time constant of coupling of beta receptors to the DNA effect (maximal effect at 6 h after isoproterenol). eactivity was lessened by 12 days of age and thereafter displayed a longer time constant (maximal effect at 12-24 h). eactivity of DNA synthesis to isoproterenol challenge was slightly different in kidney and lung (detectable by 2 days of age), but bore similar developmental characteristics to the pattern in the heart (peak of activity at 9 days and a decline in reactivity and lengthening of the time constant after 16 days). o such relationship was evident for the effects of isoproterenol on RNA or protein synthesis. hese results thus support the hypothesis that sympathetic input regulates cell replication patterns in developing peripheral organs. ecause the coupling of beta receptors to termination of DNA synthesis disappears with the maturation of physiological responses to receptor stimulation, cessation of cell replication in response to sympathetic input can occur only during a critical period in neonatal development.