Glucocorticoid enhances the response of type II cells from newborn rats to surfactant secretagogues.
There is a developmental increase in agonist-induced surfactant secretion in type II cells. The response to the P2Y(2) agonist UTP is negligible in early newborn cells but increases with age. The response to terbutaline, N-ethylcarboxyamidoadenosine (NECA), and ATP also increases with age. As glucocorticoids are known to accelerate several aspects of lung maturation we examined the effect of dexamethasone (Dex) on the response of 1-day-old rat type II cells to surfactant secretagogues. Freshly isolated cells were cultured +/-10(-6) M Dex for 18--20 h after which phosphatidylcholine secretion was measured. Dex slightly decreased the basal secretion rate. However, it significantly increased the response to terbutaline, NECA, ATP and UTP. This effect was dependent on Dex concentration (EC(50)=2-6 x 10(-9) M) and blocked by the glucocorticoid receptor antagonist RU-486. It is unlikely to be due to increased receptor content as Dex had no effect on adenylate cyclase, phospholipase C or phospholipase D activation and the response to cAMP, forskolin and phorbol ester, secretagogues acting downstream from receptors, was also increased by Dex. These data show that Dex acts directly on the type II cell to enhance the response to surfactant secretagogues, that the effect of the hormone is mediated by the glucocorticoid receptor and suggest induction of a common downstream signaling step(s). Regulation of surfactant secretion may be an important function of glucocorticoids in the developing lung.
Isohama
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Y
Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520-8064, USA.
Rooney
S A
SA
D000255:Adenosine Triphosphate / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002469:Cell Separation; D002478:Cells, Cultured; D004347:Drug Interactions; D005938:Glucocorticoids / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D011663:Pulmonary Surfactants / Q000819:agonists / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013726:Terbutaline / Q000494:pharmacology; D015854:Up-Regulation; D014544:Uridine Triphosphate / Q000494:pharmacology
D005938:Glucocorticoids; D011663:Pulmonary Surfactants; D015735:Mifepristone; D019830:Adenosine-5'-(N-ethylcarboxamide); D000255:Adenosine Triphosphate; D013726:Terbutaline; D014544:Uridine Triphosphate