A novel arginine vasopressin-binding peptide that blocks arginine vasopressin modulation of immune function.
We report on a novel peptide that blocks the neuroendocrine hormone arginine vasopressin (AVP) helper signal for IFN-gamma production by direct interaction with the hormone. The AVP-binding nonapeptide has the sequence Thr-Met-Lys-Val-Leu-Thr-Gly-Ser-Pro (binding peptide). AVP and its 6-amino acid N-terminus cyclic ring pressinoic acid (PA) are both capable of replacing the IL-2 requirement for IFN-gamma production by mouse splenic lymphocytes. We show that the AVP-binding peptide specifically and reversibly blocks AVP help in IFN-gamma production, but fails to block the helper signal of PA. Thus the intact AVP molecule and not just the N-terminal cyclic ring is important for interaction with the binding peptide. AVP interacts with the binding peptide with an apparent KD of approximately 50 nM. The AVP-binding peptide does not inhibit AVP interaction with its receptor on lymphocytes. Interestingly, whereas the AVP-binding peptide does not block the PA helper signal for IFN-gamma induction, the complex of AVP and binding peptide does reversibly block the PA signal. The AVP family of hormones requires conformational flexibility for signal transduction. Thus, we hypothesize that the AVP-binding peptide restricts this flexibility and converts AVP into an antagonist of its own action.
D000276:Adjuvants, Immunologic / Q000037:antagonists & inhibitors*; D000595:Amino Acid Sequence; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism* / Q000494:pharmacology; D001667:Binding, Competitive; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D011945:Receptors, Angiotensin / Q000187:drug effects*; D017483:Receptors, Vasopressin; D013601:T-Lymphocytes / Q000378:metabolism
D000276:Adjuvants, Immunologic; D010455:Peptides; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D007371:Interferon-gamma