Work done by us other investigators indicates that beta and alpha- adrenergic receptor number and function is decreased in the platelets and leukocytes of depressed patients, suggesting and abnormality in the receptor and postreceptor signal amplification in these illnesses. To further investigated the nature of this abnormality, we propose to study the postreceptor regulation of AC system, we will study the functions of beta-adrenergic receptors, G protein and catalytic subunit of the AC system in the platelets and leukocytes obtained from patients and controls by stimulating AC with isoproterenol, NaF forskolin an Mn++. Since the PI system and the AC system are inversely correlated, we will study thrombin, NaF stimulated inositol phosphate formation in platelets to examine if a decrease in cyclic AMP response in depressed patients is accompanied with an increased PI signalling system response. Our proposal is based on the hypotheses that there is a dysregulation of postreceptor signal amplification in depression. We specifically hypothesize that the responsiveness of G protein is decreased in the leukocytes and platelets of depressed patients and that a decrease in the reponsiveness of AC system is accompanied by an increased responsiveness o PI signalling system. An understanding of such specific abnormalities may lead us to a better understanding of the pathophysiology of these illnesses.
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