Glucocorticoid elevation of mRNA encoding epinephrine-forming enzyme in lung.
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.
Kennedy
B
B
Department of Medicine, University of California, San Diego Medical Center 92103-8341.
Elayan
H
H
Ziegler
M G
MG
D000311:Adrenal Glands / Q000378:metabolism; D000315:Adrenalectomy; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004837:Epinephrine / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D008297:Male; D010625:Phenylethanolamine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D012333:RNA, Messenger; D044005:Tetrahydroisoquinolines; D003907:Dexamethasone; C012153:7,8-dichloro-1,2,3,4-tetrahydroisoquinoline; D010625:Phenylethanolamine N-Methyltransferase; D004837:Epinephrine