Thymosin alpha 1 interacts with the VIP receptor-effector system in rat and mouse immunocompetent cells.
Thymic peptide thymosin alpha 1 (10(-11) to 10(-6) M) is shown to interact with the VIP receptor-effector system in rat and mouse peritoneal macrophages, and both rat peripheral blood lymphocytes and spleen lymphocytes. In all models, thymosin alpha 1 inhibits 125I-VIP binding with a potency that is in a range 1000-1700 times lower than that of the native VIP. Interaction of thymosin alpha 1 with VIP receptors is compared with that of some structurally VIP-related peptides such as helodermin, PHI, secretin, and glucagon. The order of potency in inhibiting 125I-VIP binding was VIP > helodermin > PHI > secretin > thymosin alpha 1. Thymosin alpha 1 (10(-10) to 10(-6) M) was weak in stimulating adenylyl cyclase activity. Its efficacy is in a range 900-1800 times lower than that of native VIP in all cell types studied. The analysis of the sequence of both complete and N-terminal portion of thymosin alpha 1 reveals close structural and physicochemical similarities with the members of the so-called VIP family of polypeptides. Taken together, experimental data support that thymosin alpha 1 must be included like the lowest partial agonist of the VIP family of polypeptides and it is a VIP receptor antagonist with weak intrinsic activity.
Pozo
D
D
Department of Medical Biochemistry and Molecular Biology, University of Seville School of Medicine, Spain.
Guerrero
J M
JM
Segura
J J
JJ
Calvo
J R
JR
D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D018005:Receptors, Vasoactive Intestinal Peptide / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D013947:Thymosin; D000242:Cyclic AMP; D000077596:Thymalfasin