Abstract
The synthetic ACTH-like decapeptide H-Val-Lys-Lys-Pro-Gly- Ser-Ser-Val-Lys-Val-OH, corresponding to amino acid residues 11-20 of the variable part of the human IgG1 heavy chain (referred to as immunocortin) was found to have an immunosuppressive effect on cells in vitro: it inhibits blast transformation of mouse thymocytes and reduces spontaneous motility of mouse peritoneal macrophages as well as their bactericidal activity against the virulent bacterial strain Salmonella typhimurium 415. Tritium-labeled immunocortin binds with high affinity to ACTH receptors on thymocytes and macrophages (Kd 2. 1 and 2.5 nM, respectively) and activates adenylate cyclase in these cells. Thus, the interaction of immunocortin with the target cell includes the following main steps: binding to the receptor, activation of adenylate cyclase, and elevation of the intracellular content of cAMP.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenylyl Cyclases / metabolism
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Adrenocorticotropic Hormone / chemistry*
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Amino Acid Sequence
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Animals
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Cells, Cultured
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Cyclic AMP / metabolism
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Humans
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Immunoglobulin G / chemistry*
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Immunoglobulin G / pharmacology*
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Immunoglobulin Heavy Chains / chemistry
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Immunoglobulin Heavy Chains / pharmacology*
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Immunosuppressive Agents / chemistry
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Immunosuppressive Agents / pharmacology*
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Lymphocyte Activation / drug effects
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Macrophages, Peritoneal / drug effects
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Macrophages, Peritoneal / immunology
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Mice
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Mice, Inbred CBA
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Peptide Fragments / chemistry
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Peptide Fragments / pharmacology*
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Rats
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Thymus Gland / cytology
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Thymus Gland / drug effects
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Thymus Gland / immunology
Substances
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Immunoglobulin G
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Immunoglobulin Heavy Chains
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Immunosuppressive Agents
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Peptide Fragments
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immunocorticotropin
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Adrenocorticotropic Hormone
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Cyclic AMP
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Adenylyl Cyclases