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TROPHIC CONTROL OF LUNG DEVELOPMENT BY SYMPATHETIC NEURONS: EFFECTS OF NEONATAL SYMPATHECTOMY WITH 6-HYDROXYDOPAMINE
Citation:
Slotkin, T., C. Lau, R. Kavlock, W. Whitmore, K. Queen, L. Orband-Miller, M. Bartolome, F. Baker, A. Cameron, L. Antolick, AND V. Bartolome. TROPHIC CONTROL OF LUNG DEVELOPMENT BY SYMPATHETIC NEURONS: EFFECTS OF NEONATAL SYMPATHECTOMY WITH 6-HYDROXYDOPAMINE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-88/539.
Description:
The onset of peripheral sympathetic neuronal function is thought to provide trophic regulatory signals for development of adrenergic target tissues. n the current study, we examined the effects on lung development of neonatal sympathectomy with hydroxydopamine. he completeness of the lesion and effectiveness in reducing sympathetic input to the tissue were confirmed by direct measurement of norepinephrine levels and turnover. Despite the denervation, no evidence of B-receptor up-regulation was found; in fact, receptor binding site tended to be reduced throughout development. The cyclic AMP response to isoproterenol challenge was initially suppressed in the lesioned animals, but become supersensitive even in the face of reduced receptor binding capabilities. Evidence was also obtained for ontogenetic abnormalities in the ornithine decarboxylase/polyamine system, which is partially controlled by B-adrenergic input and which regulates macromolecule synthesis in replicating and differentiating cells. ventually, the alterations were reflected in aberrant developmental patterns of DNA, RNA and protein in the lung. hese results indicate that sympathetic neurons influence the biochemical development of the lung and may serve to program permanently the relationships among receptor sites, receptor coupling to cellular function, and control of cell maturation.