BETA-AMYLOID PEPTIDE, SUBSTANCE-P, AND SEC RECEPTOR-LIGAND ACTIVATE CYTOPLASMIC CA2-LIKE HL-60 CELLS - EFFECT OF CHEMOTACTIC PEPTIDE ANTAGONIST BOCMLF( IN NEUTROPHIL)

It has been reported that a discrete peptide fragment of beta-amyloid protein, beta A(25-35), and neuropeptide substance P (SP) possessed se quence homology and could bind to the serine protease inhibitor (serpi n) enzyme complex (SEC) receptor. Thus, it has been thought that these peptides and SEC receptor ligand might have similar biological activi ties. In the present study, we found that C-terminal amidated beta A(2 5-35)-NH2, SP, and the SEC receptor ligand, Phe-Val-Phe-Leu-Met (FVFLM ), could induce an increase in the intracellular free Ca2+ concentrati on ([Ca2+]i) in neutrophil-like human leukemic (HL-60) cells. Pretreat ment with pertussis toxin (PTX) potently inhibited the increase in [Ca 2+](i) stimulated by these peptides, suggesting that these responses m ight be mediated by PTX-sensitive G-proteins. Furthermore, we examined the effect on these responses of t-butyloxycarbonyl-methionyl-leucyl- phenylalanine (BocMLF), which is a competitive antagonist of chemotact ic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLF) at its recep tor. BocMLF scarcely inhibited the [Ca2+](i) increase stimulated by be ta A(25-35)-NH2. However, the increase in FVFLM-induced [Ca2+](i) was potently inhibited by BocMLF. The results suggest that the [Ca2+](i) a ctivation of beta A(25-35)-NH2 may have a different mechanism from tha t of FVFLM in neutrophil-like HL-60 cells, which is not mediated by th e SEC-receptor.