title: Flaujeac factor deficiency. Reconstitution with highly purified bovine high molecular weight-kininogen and delineation of a new permeability-enhancing peptide released by plasma kallikrein from bovine high molecular weight-kininogen.
abstract: Flaujeac trait is the functional deficiency of a plasma protein of the intrinsic coagulation, kinin-forming, and plasma fibrinolytic pathways. The Flaujeac factor in man has been isolated and tentatively identified as a kininogen of high molecular weight (HMW). Highly purified bovine HMW-kininogen, but not bovine low molecular weight kininogen, repaired Flaujeac factor deficiency. The two subspecies of this molecule, HMW-kininogen a and HMW-kininogen b, also corrected Flaujeac factor deficiency. When bovine HMW-kininogen was incubated with bovine plasma kallikrein, kinin-free HMW-kininogen, bradykinin, and a glycopeptide fragment (peptide 1-2; 12,584 daltons) were rapidly released. None of these fragmentation products corrected Flaujeac factor deficiency alone or in mixtures. The function of HMW-kininogen appeared to depend upon the structural integrity of the native molecule. When injected in concentrations of 2 pmol-8 nmol/0.1 ml, peptide 1-2 caused increased vascular permeability in rabbits, rats, or guinea pigs. The enhanced permeability was maximal within 1-2 min and terminated in 5-10 min, differing from that of bradykinin or histamine. Injected together in equimolar amounts, peptide 1-2 and bradykinin produced a synergistic permeability response which was immediate in onset as well as prolonged in duration. Peptide 1-2 is a rapidly acting, highly basic glyco-peptide which mediates increased vascular permeability in a complementary and synergistic manner with bradykinin.
mesh_terms: D000818:Animals; D001778:Blood Coagulation Disorders / Q000188:drug therapy*; D001780:Blood Coagulation Tests; D001920:Bradykinin / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D002417:Cattle; D002744:Chlorpheniramine / Q000494:pharmacology; D004357:Drug Synergism; D005342:Fibrinolysis; D007610:Kallikreins / Q000097:blood*; D007704:Kininogens / Q000008:administration & dosage* / Q000097:blood; D008970:Molecular Weight; D010446:Peptide Fragments / Q000008:administration & dosage
chemical_list: D007704:Kininogens; D010446:Peptide Fragments; D002744:Chlorpheniramine; D007610:Kallikreins; D001920:Bradykinin