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 inte ract with the VIP receptor-effector system in rat and mouse peritoneal macrophages, and both rat peripheral blood lymphocytes and spleen lym phocytes. In all models, thymosin al inhibits I-125-VIP binding with a potency that is in a range 1000-1700 times lower than that of the nat ive VLP. Interaction of thymosin alpha 1 with VIP receptors is compare d with that of some structurally VIP-related peptides such as heloderm in, PHI, secretin, and glucagon. The order of potency in inhibiting I- 125-VIP binding was VIP > helodermin > PHI > secretin > thymosin alpha 1. Thymosin alpha 1 (10(-10) to 10(-6) M) was weak in stimulating ade nylyl cyclase activity. Its efficacy is in a range 900-1800 times lowe r than that of native VIP in all cell types studied. The analysis of t he sequence of both complete and N-terminal portion of thymosin al rev eals close structural and physicochemical similarities with the member s of the so-called VIP family of polypeptides. Taken together, experim ental data support that thymosin al must be included like the lowest p artial agonist of the VIP family of polypeptides and it is a VIP recep tor antagonist with weak intrinsic activity.