Study of immunosuppressive activity of a synthetic decapeptide corresponding to an ACTH-like sequence of human immunoglobulin G1.
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.
Navolotskaya
E V
EV
Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region, 142292, Russia. navolots@fibkh.serpukhov.su
Zargarova
T A
TA
Lepikhova
T N
TN
Turobov
V I
VI
Nurieva
R I
RI
Malkova
N V
NV
Lipkin
V M
VM
Zav'yalov
V P
VP
D000262:Adenylyl Cyclases / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry* / Q000494:pharmacology*; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; C082551:immunocorticotropin; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D000262:Adenylyl Cyclases