Corticosterone increases protein tyrosine kinase activity in the locus coeruleus and other monoaminergic nuclei of rat brain.
Protein tyrosine kinase was studied as a possible target of glucocorticoid action in discrete regions of rat brain. It was found that 7 days of corticosterone treatment produced a 20-25% increase in protein tyrosine kinase activity specifically in three monoaminergic nuclei known to be regulated by glucocorticoids in vivo. Thus, corticosterone increased enzyme activity in the locus coeruleus (LC), dorsal raphe, and ventral tegmentum, but not in a number of other brain regions studied. This phenomenon was characterized further in the LC. Bilateral adrenalectomy was shown to decrease protein tyrosine kinase levels in this brain region, an effect reversed completely by corticosterone replacement, indicating that this adrenal steroid plays a role in maintaining levels of the enzyme under physiological conditions in vivo. Chronic corticosterone was also found to increase levels of immunoreactivity of c-src, a well characterized protein tyrosine kinase, in the LC, results indicating that corticosterone increases protein tyrosine kinase activity in this brain region at least in part by increasing the total amount of this enzyme. Immunoblotting analysis of LC extracts with antibodies specific for phosphotyrosine indicated that the corticosterone-induced increased in protein tyrosine kinase activity in the LC is associated with a 60% increase in the incorporation of phosphotyrosine into endogenous proteins. The results demonstrate that protein tyrosine kinase activity is regulated by glucocorticoids in discrete regions of the central nervous system and raise the possibility that regulation of these brain regions by glucocorticoids is mediated in part through effects on this enzyme.
Nestler
E J
EJ
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06508.
Terwilliger
R Z
RZ
Halm
E
E
D000315:Adrenalectomy; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D003345:Corticosterone / Q000494:pharmacology*; D008125:Locus Coeruleus / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D011506:Proteins / Q000378:metabolism; D011519:Proto-Oncogenes; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D011506:Proteins; D011505:Protein-Tyrosine Kinases; D003345:Corticosterone