AJP - Lung Cellular and Molecular Physiology, Vol 265, Issue 2 117-L120, Copyright © 1993 by American Physiological Society

ARTICLES

Glucocorticoid elevation of mRNA encoding epinephrine-forming enzyme in lung

B. Kennedy, H. Elayan and M. G. Ziegler
Department of Medicine, University of California, San Diego Medical Center 92103-8341.

The epinephrine-forming enzyme phenylethanolamine N-methyltransferase (PNMT) is present in lung and its activity is increased by the glucocorticoid dexamethasone. Chronic administration of dexamethasone (0.5 mg/kg twice daily) doubled levels of mRNA coding for PNMT in rat lung. Administration of the glucocorticoid antagonist RU 486 after 7 days of dexamethasone treated reduced PNMT mRNA by about two-thirds within 24 h. Lung epinephrine (E) levels correlated with lung PNMT activity in these dexamethasone-treated and control rats. In a separate experiment, lung PNMT mRNA levels were nearly tripled 6 h after dexamethasone (1 mg/kg sc). In a third experiment chronic administration of the PNMT inhibitor SKF 64139 (50 mg/kg twice daily) reduced in vitro lung PNMT activity in chronically dexamethasone-treated adrenalectomized rats by approximately 96% and reduced lung E levels by approximately 75%. We conclude that glucocorticoids increase lung PNMT activity by increasing levels of mRNA coding for this enzyme. The data also suggest that a substantial fraction of lung E is locally synthesized. We speculate that enhanced lung E synthesis may participate in glucocorticoid-induced dilation of the bronchioles.

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				O. Krizanova, L. Micutkova, J. Jelokova, M. Filipenko, E. Sabban, and R. Kvetnansky Existence of cardiac PNMT mRNA in adult rats: elevation by stress in a glucocorticoid-dependent manner Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1372 - H1379. [Abstract] [Full Text] [PDF]