title: Partial agonists and full antagonists at the human and murine bradykinin B1 receptors.
abstract: We developed a functional assay to evaluate the activity of kinin peptides at the human and mouse bradykinin (BK) B1 receptors. The photoprotein aequorin expressed in 293-AEQ17 cells was used to measure calcium mobilization due to activation of the human or mouse B1 receptors by kinin peptides. The B1 agonists des-Arg9-BK and des-Arg10-kallidin activated the human receptor (EC50 = 112 and 5 nM, respectively), whereas the B1 peptide antagonists des-Arg9,Leu8-BK and des-Arg10,Leu9-kallidin showed no activation. At the murine receptor, the agonists des-Arg9-BK and des-Arg10-kallidin activated the receptor with EC50 values of 39 and 23 nM, respectively. In contrast, the two peptide antagonists showed significant agonism at the murine receptor. Thirty-nine and 44% agonism of the mouse receptor was observed with des-Arg9,Leu8-BK (EC50 = 56 nM) and des-Arg10,Leu9-kallidin (EC50 = 177 nM). Two recently described kinin analogues, [Lys-Lys0,Hyp3,Igl5,D-Igl7,Oic8,des-Arg9]B K and [D-Arg0,Hyp3,Igl5,D-Igl7, Oic8,des-Arg9]BK (B9858 and des-Arg9-B9430), failed to agonize the mouse receptor. These peptides were potent antagonists of des-Arg10-kallidin- and des-Arg9-BK-induced bioluminescence at the cloned human and mouse B1 receptors.
authors.affiliation: Department of Genetics and Molecular Biology, Merck Research Laboratories, Rahway, NJ 07065, USA.
authors.forename: T
authors.initials: T
authors.lastname: MacNeil
authors.forename: S
authors.initials: S
authors.lastname: Feighner
authors.forename: D L
authors.initials: DL
authors.lastname: Hreniuk
authors.forename: J F
authors.initials: JF
authors.lastname: Hess
authors.forename: L H
authors.initials: LH
authors.lastname: Van der Ploeg
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D019556:COS Cells / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D051379:Mice; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists* / Q000378:metabolism; D013045:Species Specificity
chemical_list: D065168:Bradykinin Receptor Antagonists; D010455:Peptides; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D001920:Bradykinin