Disease relevance of Ile-ser-bradykinin

• Degradation of Ile-Ser-Bradykinin by enzymes in human serum and ascites [1].
• In contrast, treatment of plasma from healthy human subjects (n = 8) and from patients (n = 8) with inflammation due to acute or chronic gastrointestinal disease under the same conditions did not generate any detectable T-kinin immunoreactivity [2].
• The edema produced by the injection of carrageenan in rat hindpaws was associated with a sevenfold increase of immunoreactive kinins in the inflamed paw extract (from 0.021 +/- 0.007 to 0.141 +/- 0.021 pmol/g tissue; p < 0.01), the immunoreactivity corresponded to BK, kallidin, and T-kinin after HPLC separation [3].
• T-kinin in human ovarian carcinoma ascites [4].
• 3. T-kinin may not be involved in these inflammations, since the deficient strain owns normal plasma level of T-kininogen [5].

High impact information on Ile-ser-bradykinin

• In the intron downstream of the exon coding for Ile-Ser-bradykinin, the two alpha 1-MAP genes contained sequence sections similar to the section in the human kininogen gene which codes for the carboxyl-terminal chain of high molecular weight kininogen [6].
• The deduced amino acid sequences indicated that one, termed K-prekininogen, represents the counterpart of the known low molecular weight prekininogen present in other mammals, while the other two, called T-prekininogens, contain a novel T-kinin sequence which was recently identified from rat plasma [7].
• T-kininogen, the major kininogen in rat plasma, releases Ile-Ser-bradykinin (T-kinin) when incubated with trypsin, but is not a substrate for tissue kallikrein [8].
• Antigen gamma released a kinin which was identified as T-kinin by reverse-phase h.p.l.c. The T-kininogenase activity of antigen gamma had a Km of 29 +/- 4 microM and a kcat/Km of 140 M-1.s-1, and was comparable with its high and low molecular mass-kininogenase activity (7.4 and 10 micrograms of kinin/h per mg respectively) [8].
• While the potency of T-kinin on rat uterus contraction was similar to that of bradykinin, binding studies showed that the affinity of T-kinin to the receptor was 10-fold lower than that of bradykinin [9].

Biological context of Ile-ser-bradykinin

• Effect of T-kinin on microvascular permeability and its modulation by peptidases in rat airways [10].
• T-kinin is resistant to hydrolysis by angiotensin I-converting enzyme [11].
• In the conscious, unrestrained rat, intrathecal (i.t.) injection of 0.81 pmol-81 nmol bradykinin (BK), kallidin (KD) and T-kinin at the T-9 spinal cord level produced transient (less than 10 min) increases in mean arterial pressure (MAP) and longer lasting decreases in heart rate (HR) [12].

Anatomical context of Ile-ser-bradykinin

• This study characterizes the receptors involved in T-kinin activity on both the intact isolated rat uterus and membrane receptor preparations of the rat uterus [9].
• 6. We conclude that the role of T-kininogen in this kind of exudate was mainly the inhibition of thiol proteinases and not the release of T-kinin [13].
• The pharmacology of T-kinin and des-Arg(11)-T-kinin in primary cultures of rat bladder smooth muscle cells [14].
• Intravenous injection of T-kinin (0.1-10 mumol/kg) increased dye extravasation in a dose-dependent manner, with 134% for trachea and 117% for bronchi by 1 mumol/kg [10].
• The distribution of T-kininogen throughout the central and peripheral nervous system of the rat, the variations of its level during the life span suggest that T-kininogen would play the role of a cysteine proteinase inhibitor and not that of a T-kinin-releasing substrate in nervous tissues [15].

Associations of Ile-ser-bradykinin with other chemical compounds

• Trypsin treatment of the kininogen in traumatized cord released both bradykinin and T-kinin, which were separated by HPLC and quantified with a kinin radioimmunoassay [16].
• The kinin isolated by n-butanol extraction was separated by reverse-phase high-performance liquid chromatography into T-kinin and a T-kinin derivative [17].
• We examined the effect of T-kinin on vascular permeability in airways of anesthetized rats in vivo by using photometric measurement of the extravasated Evans blue [10].
• The final material had a single N-terminal isoleucine and was shown by amino acid analysis and sequence determination to have the structure of the undecapeptide Ile-Ser-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg (isoleucyl-seryl-bradykinin) [18].
• The increase in total TRSS was due to substances which elicit the slow contraction of the isolated guinea pig ileum and which could be distinguished from BK, T-kinin and other BK homologues by gel filtration on Sephadex G-25, gradient elution chromatography on CM-cellulose and by the slow rate of contraction of the guinea pig ileum [19].

Gene context of Ile-ser-bradykinin

• These results indicate for the first time that free T-kinin as well as bradykinin is released during an inflammatory response in rat and confirms our previous finding that T-kininogen may be a major acute-phase protein in inflammation [20].
• The results show that T-kinin acts through kinin B2 receptors in the rat uterus as demonstrated by B2 receptor-antagonist inhibition [9].
• 3. The analogues Ile-Ser-Bk (T-kinin) and Lys-Lys-Bk, which interact with both B1 and B2 Bk receptors, produced pressor effects similar to those of Bk, although of greater duration, whereas des-Arg9-Bk, a B1-receptor agonist, had no effect [21].
• Cathepsin D alone could not release T-kinin, but T-kinin-containing peptides [22].
• Changes in plasma extravasation were quantified by counting the number of leaky sites and calculating the clearance of fluorescein isothiocyanate- (FITC) dextran (mol mass = 70 kDa) during suffusion of the cheek pouch with T-kinin (0.1-1.0 microM) by using intravital microscopy [23].

Analytical, diagnostic and therapeutic context of Ile-ser-bradykinin

• The enzyme cleaves T-kininogen to release T-kinin which was separated by high performance liquid chromatography on a reverse phase C18 column and identified by a kinin radioimmunoassay [24].
• Bioassays showed that the T-kinin moiety was retained in T-kininogen [13].
• Kininogen partially purified from rat urine by affinity chromatography using S-carboxymethylated papain-agarose liberated only T-kinin upon trypsinization, but not upon treatment with rat glandular kallikreins [25].
• Measurement of T-kinin in rat plasma using a specific radioimmunoassay [2].
• Under constant-flow conditions, injection of T-kinin and bradykinin into the perfusion circuit induced similar dose-related decreases in perfusion pressure [26].

References