title: A peptide with unique receptor specificity: stimulation of phosphoinositide hydrolysis and induction of superoxide generation in human neutrophils.
abstract: Previously, we identified peptides that stimulate phosphoinositide hydrolysis in several leukocyte cell lines from mixtures of random hexapeptide sequences. Moreover, the peptides activate phospholipase C via a pertussis toxin-sensitive G protein-coupled receptor. We now investigate the structure-activity relationship of the peptides with the goal of improving the activity of the peptides, as well as the biologic function of the peptides. Substitution of the L-methionine at the C terminus of peptides with D-methionine markedly increased the effectiveness of the peptides. The half-maximal effective concentrations of MKYMPm-NH2 and WKYMVm-NH2 for stimulation of phosphoinositide hydrolysis in U266 cells were 30 and 0.5 nM, respectively. By BIAcore analysis we confirmed the existence of a receptor for WKYMVm-NH2. Furthermore, the intracellular calcium concentration increase induced by WKYMVm-NH2 was not inhibited by several chemoattractants (FMLP, IL-8, platelet-activating factor, C5a, granulocyte-macrophage CSF, and granulocyte CSF) suggests that WKYMVm-NH2 has a unique cell surface receptor on leukocytes. WKYMVm-NH2 stimulated the phosphoinositide hydrolysis in U937, HL60, and U266 cells, as well as in human neutrophils. Moreover, WKYMVm-NH2 is more effective than FMLP in the production of superoxide in human neutrophils. The data suggest that WKYMVm-NH2 may have the ability to activate the microbicidal functions of human neutrophils.
authors.affiliation: Department of Life Science, Pohang University of Science and Technology, Hyojadong, Korea.
authors.forename: J K
authors.initials: JK
authors.lastname: Seo
authors.forename: S Y
authors.initials: SY
authors.lastname: Choi
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.forename: S H
authors.initials: SH
authors.lastname: Baek
authors.forename: K T
authors.initials: KT
authors.lastname: Kim
authors.forename: C B
authors.initials: CB
authors.lastname: Chae
authors.forename: J D
authors.initials: JD
authors.lastname: Lambeth
authors.forename: P G
authors.initials: PG
authors.lastname: Suh
authors.forename: S H
authors.initials: SH
authors.lastname: Ryu
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D015374:Biosensing Techniques; D002118:Calcium / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis; D007424:Intracellular Fluid / Q000378:metabolism; D016393:Lymphoma, B-Cell; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism / Q000502:physiology*; D017384:Sequence Deletion; D013237:Stereoisomerism; D013481:Superoxides / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000596:Amino Acids; D009842:Oligopeptides; D010716:Phosphatidylinositols; D018000:Receptors, Peptide; D013481:Superoxides; D002118:Calcium; D005998:Glycine