AJP - Cell Physiology, Vol 265, Issue 4 C1046-C1049, Copyright © 1993 by American Physiological Society

ARTICLES

Angiotensin II type 1 receptor-mediated stimulation of c-fos gene expression in astroglial cultures

M. K. Raizada, B. Rydzewski, D. Lu and C. Sumners
Department of Physiology, University of Florida College of Medicine, Gainesville 32610.

Angiotensin II (ANG II) stimulates plasminogen activator inhibitor 1 (PAI-1) gene expression in astroglial cells prepared from rat brains. In this study, we investigated whether c-fos gene expression may be involved in this cellular action of ANG II. Incubation of astroglial cultures with ANG II caused a time- and dose-dependent transient stimulation of the steady-state levels of c-fos mRNA, with a maximal stimulation of 50-fold observed with 100 nM ANG II within 30-45 min. This stimulation was completely abolished by the presence of the type 1 ANG II (AT1) receptor antagonist losartan but not by the type 2 ANG II receptor blocker PD-123177. Depolarization of brain cell cultures with 50 mM K+ also caused a 100-fold increase in c-fos mRNA levels, an effect partially blocked by losartan. These observations show that AT1 receptor activation stimulates expression of the c-fos gene, which may act as a third messenger in the regulation of cellular actions of ANG II, including PAI-1 gene expression in astroglial cells.

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