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TA Slotkin, WL Whitmore, L Orband-Miller, KL Queen and K Haim
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina.
The sympathetic nervous system has been hypothesized to coordinate the timing of cellular development in peripheral tissues. In 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. The 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. The developmental decline in DNA synthesis in heart, kidney and lung coincided with the maturation of sympathetic projections. Direct stimulation of beta receptors by the in vivo administration of isoproterenol caused acute reductions in DNA synthesis in an age-dependent manner. In 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). Reactivity was lessened by 12 days of age and thereafter displayed a longer time constant (maximal effect at 12-24 h). Reactivity 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 reactivity at 9 days and a decline in reactivity and lengthening of the time constant after 16 days).(ABSTRACT TRUNCATED AT 250 WORDS)
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