The overall objective of the proposed research is to study the regulatory biochemical functions of glucocorticoids in the brain. Three areas will be explored: First, we will determine the effects of glucocorticoids in vitro on adenylate cyclase and high affinity calcium binding in synaptic (synaptosomal) plasma membrane from rat brain. In order to evaluate the specificity of the steroid effects on membrane, Na, K-ATPase and 5 feet-nucleotidase will be monitored as membrane marker enzymes. Second, we will determine the role of ATP in the regulation of cytosol glucocorticoid receptor from the brain. Third, we will determine the effects of glucocorticoids on the activity of a brain protein kinase, and attempt to relate this protein kinase to the activation of tryptophan hydroxylase in conjunction with the hormonal effects. Since this brain protein kinase is an enzyme still poorly known, we will purify and characterize this enzyme as a necessary step in order to understand the regulatory effects of the hormone. Adrenal glucocorticoids are one of the major factors regulating the physiological responses to environmental stress. The basic knowledge that we plan to seek will contribute to the understanding of the stress effects on brain.
