In recent years, it has been suggested that the ability of the nervous and immune systems to influence each other's function may be the result of ligands and receptors common to both systems. Evidence to support this hypothesis comes from the findings that lymphocytes have the ability to produce many of the neuroendocrine hormones including ACTH and the endorphins; however, direct biochemical evidence for the presence of common receptors on cells of the nervous and immune systems is lacking. Thus, the purpose of this proposal is to demonstrate that one particular receptor, the lymphocyte ACTH receptor, is identical with respect to its structure and ligand binding ability when compared to its adrenal counterpart. In our laboratory, adrenal ACTH receptors have been previously isolated and characterized with respect to their subunit structure and ability to bind ACTH using an antibody specific for the receptor. Similar studies are proposed for the lymphocyte ACTH receptor using immunoaffinity chromatography to isolate the receptors and subsequent analysis of the structure on polyacrylamide gels. By comparing the molecular characteristics of the adrenal ACTH receptor with those obtained from the lymphocyte receptor, it will be possible to determine if the two receptors are similar. While the adrenal ACTH receptor functions to increase steroidogenesis in adrenal cells, the function of the lymphocyte ACTH receptor is unknown. We propose to investigate the function of the lymphocyte ACTH receptor at a molecular level by following the modulation of receptors after stimulation of lymphocytes with ACTH, mitogens, antigen, or selected lymphokines. After stimulation, the expression of surface receptors will be followed using immunofluorescent techniques and subsequent flow cytometric analysis. Studies will also investigate the effects of ACTH binding on cyclic nucleotide levels and protein phosphorylation in lymphocytes. ACTH receptor function will be addressed by comparing biological responses of lymphocytes treated with anti-receptor antibody versus ACTH-treated cells. Thus, the overall objective of this proposal is to compare the molecular structure of the lymphocyte with that of its adrenal counterpart, and to explore the function of the lymphocyte ACTH receptor at a molecular level.
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