Adrenal glucocorticoids modulate [H-3]cyclic AMP binding to protein kinasea (PKA), cyclic AMP-cependent PKA activity, and protein levels of selective regulatory and catalytic subunit isoforms of PKA in rat brain
Y. Dwivedi et Gn. Pandey, Adrenal glucocorticoids modulate [H-3]cyclic AMP binding to protein kinasea (PKA), cyclic AMP-cependent PKA activity, and protein levels of selective regulatory and catalytic subunit isoforms of PKA in rat brain, J PHARM EXP, 294(1), 2000, pp. 103-116
Citations number
51
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Alterations in hypothalamic-pituitary-adrenal (HPA) function are associated
with changes in mood and behavior. Protein kinase A (PKA), on activation,
phosphorylates many important intracellular proteins and thereby plays a ma
jor role in mediating various physiological functions in brain. We systemat
ically examined the relationship of altered HPA function with PKA modificat
ions in rat brain after administering corticosterone to normal rats and by
first adrenalectomizing rats and then simultaneously treating them with dif
ferent doses of corticosterone. Rats were decapitated on day 1, 4, or 14. S
ubcutaneously implanted 50- or 100-mg corticosterone pellets in normal rats
for 4 or 14 days significantly decreased PKA activity, B-max of [H-3]cycli
c AMP binding, and protein levels of selective PKA regulatory (RI alpha, RI
I beta) and catalytic (Cat beta) subunit isoforms in cortex and hippocampus
in a dose-dependent manner without any significant changes at day 1; these
changes were more pronounced at day 14. However, adrenalectomy caused the
opposite changes in these measures at day 4 or 14 in both cortex and hippoc
ampus, and the magnitude of the changes was more pronounced at day 14. Simu
ltaneous treatment with implanted corticosterone at 50- or 100-mg doses in
adrenalectomized rats reversed the adrenalectomy-induced increases in PKA m
easures in a dose-dependent manner. These results suggest that endogenous g
lucocorticoid modifies the expression of RI alpha, RII alpha, and Cat beta
subunit isoforms of PKA, as well as the catalytic and regulatory activities
of PKA, and that these alterations in PKA may in part explain HPA axis-med
iated changes in mood and behavior.