Functionally active high molecular weight-kininogen was found in the liver, but not in the plasma of brown Norway Katholiek rat.
Plasma and liver levels of high molecular weight (HMW-) kininogen were assessed by a newly developed radioimmunoassay in B/N-Katholiek strain rats, which is congenitally deficient in plasma HMW- and low molecular weight (LMW-) kininogens. The plasma level of immuno-reactive HMW-kiniogen in this strain was about 4% of that of the normal strain, B/N-Kitasato, whereas its level in B/N-Katholiek liver was approximately 60% of that in normal strain liver. There was no significant difference of half-life of HMW-kininogen in the circulating blood between the deficient and normal rats. When secretion of HMW-kiniogen from the liver cells of the two strains was examined by primary culture of their hepatocytes, the hepatocytes from the deficient strain did not secrete HMW-kininogen in the medium. HMW-kininogens were isolated from the liver microsomal fractions of both strains by use of an immuno-affinity column. The isolated protein from B/N-Katholiek liver showed similar mobility on SDS-PAGE to that from normal rat liver, and had biological activities of HMW-kininogen purified from normal rat plasma, such as intrinsic blood clotting cofactor, thiol-proteinase inhibitor, and kinin precursor. These results indicate that the plasma deficiency in the B/N-Katholiek strain is due to a defect of HMW-kininogen secretion from the liver.
Hayashi
I
I
Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Maruhashi
J
J
Oh-ishi
S
S
D000818:Animals; D002478:Cells, Cultured; D006207:Half-Life; D007704:Kininogens / Q000097:blood / Q000172:deficiency / Q000378:metabolism*; D007705:Kinins / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D008970:Molecular Weight; D051381:Rats; D011914:Rats, Inbred BN; D011922:Rats, Mutant Strains
D007704:Kininogens; D007705:Kinins