Synthetic ACTH-Like Peptide GKVLKKRR, Corresponding to the Fragment 81-88 of Human Pro-Interleukin-l alpha, Acts as an Antagonist of ACTH Receptor

摘要

We have previously found that the fragment 81-88 (GKVLKKRR) of human pro-interleukin-la (pIL-loc) has more than 80% homology with the fragment 10-18 (GKPVGKKRR) of adrenocortico-tropic hormone (ACTH). We have synthesized the octapeptide GKVLKKRR (referred to as leukocor-ticotropin, LCT) and shown that it binds to the ACTH receptor on mouse splenocytes and macro-phages with high affinity and specificity (Zav'yalov et al., 1995). The main function of ACTH is the stimulation of synthesis and secretion of glucocor-ticoids by adrenal zona fasciculata/reticularis cells. The sensitivity of adrenal cortex cells to ACTH depends on the expression and function of the G-protein-coupled receptor (melanocortin-2 receptor, MC2R), which belongs to the melanocortin receptor subfamily (Cone et al., 1993; Clark et al., 2003; Beuschlein et al., 2001; Voisey et al., 2003).