Cyclic amp modulates glucocorticoid-induced protein accumulation
and glucocorticoid receptor in cardiomyocytes.
Sato, Atsuhisa, Karen E. Sheppard, Meryl J. Fullerton, and John W.
Funder.
Baker Medical Research Institute, Melbourne, Australia
APStracts 3:0149E, 1996.
Glucocorticoids have complex effects on cardiac muscle growth in vivo,
and one possible reason may be the regulatory cross-talk between
glucocorticoids and second messengers. In this study, we have
investigated the effect of cyclic AMP (cAMP), shown to affect
cardiomyocyte growth and glucocorticoid action in several systems, on
glucocorticoid-induced protein accumulation and glucocorticoid
receptor (GR) in neonatal rat cardiomyocytes. Dexamethasone (DEX)
decreased protein/DNA ratio, and 8-bromo-cyclic AMP (BrcAMP) or
forskolin increased this ratio. The inhibitory effect of DEX was
potentiated by an elevated cAMP, despite the stimulatory effect of
cAMP alone. Nuclear GR binding was increased by BrcAMP, with no
change in GR mRNA or protein levels, via increased affinity of
nuclear GR. H89 blocked the effects of BrcAMP. In conclusion,
glucocorticoids have an inhibitory effect on protein accumulation in
cardiomyocytes via GR, an effect potentiated by elevated cAMP via
increased nuclear GR binding. These results suggest that
glucocorticoid effects on cardiomyocytes may be modulated by cAMP
-mediated mechanisms, which may produce the complex effects of
glucocorticoids on cardiomyocyte growth in vivo.
Received 2 February 1996; accepted in final form 15 July 1996.
APS Manuscript Number E62-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996