||Trophic Control of Lung Development by Sympathetic Neurons: Effects of Neonatal Sympathectomy with 6-Hydroxydopamine.
Slotkin, T. A. ;
Lau, C. ;
Kavlock, R. J. ;
Whitmore, W. L. ;
Queen., K. L. ;
||Northrop Services, Inc., Research Triangle Park, NC. ;Duke Univ. Medical Center, Durham, NC. Dept. of Pharmacology.;Health Effects Research Lab., Research Triangle Park, NC.
||EPA-68-02-4450, EPA-R-813769; EPA/600/J-88/539;
Nerve cells ;
Ribonucleic acids ;
Deoxyribonucleic acids ;
Body weight ;
Sympathetic nervous system ;
Chemical sympathectomy ;
Newborn animals ;
Beta adrenergic receptors,Ornithine decarboxylase ;
Cyclic AMP ;
||Some EPA libraries have a fiche copy filed under the call number shown.
||The onset of peripheral sympathetic neuronal function is thought to provide trophic regulatory signals for development of adrenergic target tissues. In the current study, the effects on lung development of neonaatal sympathectomy with 6-hydroxydopamine were examined. The 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 beta-receptor up-regulation was found; in fact, receptor binding sites tended to be reduced throughout development. The cyclic AMP response to isoproterenol challenge was initially suppressed in the lesioned animals, but became 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 beta-adrenergic input and which regulates macromolecule synthesis in replicating and differentiating cells. Eventually, the alterations were reflected in aberrant developmental patterns of DNA, RNA and protein in the lung. These 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.
||Pub. in Jnl. of Developmental Physiology, v10 p577-590 Sep 88. See also PB90-217464. Prepared in cooperation with Duke Univ. Medical Center, Durham, NC. Dept. of Pharmacology. Sponsored by Health Effects Research Lab., Research Triangle Park, NC.
|NTIS Title Notes
||Reprint: Trophic Control of Lung Development by Sympathetic Neurons: Effects of Neonatal Sympathectomy with 6-Hydroxydopamine.
||PC A03/MF A01