Receptor-binding properties of the peptides corresponding to the β-endorphin-like sequence of human immunoglobulin G

The decapeptide H 2N-Ser-Leu-Thr-Cys-Leu-Val-Lys-Gly-Phe-Tyr-COOH (termed immunorphin) corresponding to the sequence 364–373 of the CH 3 domain of the human immunoglobulin G1 Eu heavy chain and displaying a 43% identity with the antigenic determinant of β-endorphin was synthesized. Immunorphin was found to compete with 125I-β-endorphin for high-affinity receptors on murine peritoneal macrophages ( K = 2.5 ± 0.9 × 10 −9 M) and with 3H-morphin for receptors on murine thymocytes ( K i = 2.7 ± 0.6 × 10 −9 M) and murine macrophages ( K i = 5.9 ± 0.7 × 10 −9M). In particular two types of receptors to 125I-β-endorphin with K d1 = 6.1 ± 0.6 × 10 −9 M and K d2 = 3.1 ± 0.2 × 10 −8 M were revealed on macrophages. The second type of receptors interacted with 125I-β-endorphin, 3H-Met-enkephalin, 3H-Leu-enkephalin and 3H-morphin; the first displayed reactivity with 125I-β-endorphin, 3H-morphin and immunorphin. The first type receptors are not present on murine brain cells nor are inhibited by naloxone. A minimum fragment of immunorphin practically completely retaining its inhibitory activity in the competition tests with 125I-β-endorphin for common receptors on thymocytes was found to correspond to the tetrapeptide H 2N-Lys-Gly-Phe-Tyr-COOH ( K i = 5.6 ± 0.5 × 10 −9 M).