title: Rat tissue kallikrein releases a kallidin-like peptide from rat low-molecular-weight kininogen.
abstract: The kallikrein-kinin system is subdivided into the plasma and tissue-kallikrein-kinin system, with bradykinin (BK) and kallidin (KAL) (Lys(0)-bradykinin) as functional peptides. This occurs in both humans and other mammals. Both peptides are released by plasma and tissue-kallikrein. BK, but not KAL, has been detected in rats until now. One can explain this observation by the structural differences found in the sequence of rat high- and low-molecular kininogen containing an Arg-residue instead of a Lys-residue in front of the N-terminus of the BK sequence. Nevertheless, we were able to measure a kallidin-like peptide (KLP), in rat plasma and urine, using a specific KAL antiserum. In order to confirm our data, we isolated low-molecular-weight kininogen from rat plasma and incubated it with purified rat glandular kallikrein. The generated peptide was retained on a high-pressure liquid chromatography column and displaced by an excess of angiotensin I. The KLP-containing fraction was identified with the KLP radioimmunoassay. A specific ion signal with a mass to charge ratio (m/z) of 1216.73 was detected with matrix-assisted laser desorption/ionization mass spectrometry. As proposed earlier, the structure of this peptide is Arg(1)-KAL, instead of Lys(1)-KAL. The structural similarity between the Lys- and the Arg-residue explains the high crossreactivity (80%) of KLP with the specific KAL antibody. The incubation of KLP with angiotensin-converting enzyme yields two molecules with masses of 913.4 and 729.3 containing the sequence H-Arg-Arg-Pro-Pro-Gly-Phe-Ser-Pro-OH and H-Arg-Arg-Pro-Pro-Gly-Phe-OH. The enzymatic cleavage could be inhibited by captopril. The data suggest that in rats, as in other mammals, the tissue kallikrein-kinin system mediates its physiological effects via a kallidin-like peptide, which is Arg(1)-kallidin (Arg(0)-bradykinin).
authors.affiliation: Department of Pharmaceutical Pharmacology, Institute of Pharmacology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 366, D-69120 Heidelberg, Germany. ulrich.hilgenfeldt@urz.uni-heidelberg.de
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hilgenfeldt
authors.forename: Christina
authors.initials: C
authors.lastname: Stannek
authors.forename: Martina
authors.initials: M
authors.lastname: Lukasova
authors.forename: Martina
authors.initials: M
authors.lastname: Schnölzer
authors.forename: Sabina
authors.initials: S
authors.lastname: Lewicka
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007609:Kallidin / Q000302:isolation & purification* / Q000378:metabolism / Q000652:urine; D019728:Kininogen, Low-Molecular-Weight / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020840:Tissue Kallikreins / Q000502:physiology*
chemical_list: D019728:Kininogen, Low-Molecular-Weight; D007609:Kallidin; D007703:Peptidyl-Dipeptidase A; D020840:Tissue Kallikreins; D001920:Bradykinin