ACTH receptor-mediated induction of leukocyte cyclic AMP.
Studies were conducted to determine whether lymphocyte ACTH receptors behave as their structurally similar adrenal cell counterparts, in terms of adenylate cyclase activation and cyclic AMP (cAMP) production in the presence of ACTH. Treatment of mouse mononuclear splenocytes with ACTH (10(-5) to 10(-10) M) induced a consistent rise in cAMP. ACTH treatment of more homogenous cell populations, represented by Molt 4 T lymphoblast and S49A T cell lymphoma lines, yielded a dramatic, dose-related increase in cAMP levels for S49A cells but not for Molt 4 cells. Immunofluorescence assays, employing an antiserum to the adrenal cell ACTH receptor, indicated that 45% of splenocytes, 69% of S49A cells, and less than 1% of Molt 4 cells possess ACTH receptors. Radioligand binding studies confirmed that Molt 4 cells possess many fewer receptors than S49A cells, and probably fail to respond to ACTH because they lack the appropriate receptor. This is the first report of ACTH induction of leukocyte cAMP, evidence important to understanding the mechanisms by which this neuroendocrine hormone influences immune responses.
Johnson
E W
EW
Department of Microbiology, University of Texas Medical Branch, Galveston 77550.
Blalock
J E
JE
Smith
E M
EM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000311:Adrenal Glands / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005455:Fluorescent Antibody Technique; D007962:Leukocytes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018043:Receptors, Corticotropin; D011979:Receptors, Pituitary Hormone / Q000502:physiology*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018043:Receptors, Corticotropin; D011979:Receptors, Pituitary Hormone; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D000262:Adenylyl Cyclases