Disease relevance of KALLIDIN

• We conclude, therefore, that glandular kallikrein is secreted during the allergic response and can contribute to the formation of the lysylbradykinin produced during the allergic reaction [1].
• Using epithelial monolayers of HCA-7 cells, derived from a primary human colonic adenocarcinoma and grown on pervious supports, it is shown that responses to lysylbradykinin can be elicited from either side [2].
• To investigate the interaction between arginine-vasopressin (AVP) and the renal kallikrein-kinin system (KKS), urinary excretion rates of bradykinin (BK) and lysyl-bradykinin (LBK) were monitored in humans following water-loading, and in conscious diabetes insipidus (DI) rats during the infusion of AVP [3].

High impact information on KALLIDIN

• The antibodies were isotyped as IgG1, kappa-type, and their target epitopes mapped with bradykinin, lysyl-bradykinin (kallidin), kinin receptor antagonists, and fragments thereof, revealing three distinct sets of mAb, i.e., mAb against bradykinin (MBK)1, MBK2, and MBK3 [4].
• The activity of the aminopeptidase against its synthetic substrate was also inhibited by lysylbradykinin (IC50 = 50 microM) [5].
• Electrogenic ion transport can be stimulated by the beta-adrenergic agonist isoproterenol (10(-6) M) and by lysylbradykinin (10(-7) M) but not by the cholinergic agonist carbachol at 10(-6) M) [6].
• High molecular weight Kgn and low molecular weight Kgn were both diminished in MH (0.26 +/- 0.04 nmol bradykinin/ml and 0.93 +/- 0.12 nmol lysyl-bradykinin/ml, respectively) as compared to NC (0.39 +/- 0.07 and 1.92 +/- 0.16) and EH (0.51 +/- 0.07 and 1.65 +/- 0.13) [7].
• We have synthesized internally quenched peptides spanning the Met379-Lys380 or Arg389-Ser390 bonds of human kininogen (hkng) that flank lysyl-bradykinin and have studied the kinetics of their hydrolysis by human tissue kallikrein [8].

Biological context of KALLIDIN

• Lysyl-bradykinin (LBK) hydrolysis (kininase activity) was measured by radioimmunoassay [9].
• The pressor and heart rate responses to epicardial kallikrein were slower in onset and longer lasting than those evoked by bradykinin or lysyl-bradykinin [10].
• This sequence shows two amino acid substitutions (Phe6-->Trp and Phe9-->Leu) compared with mammalian lysyl-bradykinin (kallidin) [11].
• The results demonstrate that kinins, particularly LBK, have bimodal effects on the renal vascular resistance of the isolated perfused rat kidney [12].
• Peptidase inhibitors potentiate lysylbradykinin-induced bronchoconstriction in the rat [13].

Anatomical context of KALLIDIN

• 1. Reflexogenic effects of bradykinin, lysyl-bradykinin and endogenously formed kinins on neural afferents of the left ventricular epicardium were studied in anaesthetized, open-chest dogs [10].
• Sheet cultures prepared from sweat gland coils also showed SCC responses to both carbachol and LBK [14].
• 1. Hoe-140, a potent kinin receptor antagonist, was investigated for its ability to inhibit the effects of lysylbradykinin (kallidin) on a cultured colonic epithelium, HCA-7 Colony 29, derived from a human adenocarcinoma [15].
• Activation of ion channels by lysylbradykinin in the HCA-7 colony 29 human adenocarcinoma cell line [16].
• To determine whether these peptidases play roles in modulating kinin-induced contractions in the airways, we studied the effects of captopril, an ACE inhibitor, and of leucine-thiorphan and phosphoramidon, two NEP inhibitors, on the contractile responses to bradykinin and lysyl-bradykinin in isolated segments of ferret trachea [17].

Associations of KALLIDIN with other chemical compounds

• 2. Measurements of electrogenic chloride secretion (as short circuit current), and of intracellular Ca2+ (from Fura-2 fluorescence) were used to assess the action of lysylbradykinin in the absence and presence of Hoe 140 [15].
• A cultured human epithelial cell line, Colony 29, has been used to investigate the relation between anion secretion and intracellular Ca2+ concentration (Cai) in response to the secretagogues, lysylbradykinin (LBk) and histamine [18].
• These enzymes release the vasoactive peptides angiotensin II and lysyl-bradykinin from the precursors angiotensinogen and kininogen, respectively [19].
• The effect of the kinin, kallidin (lysyl-bradykinin) on phosphoinositide metabolism and prolactin secretion was examined in male rat anterior pituitary cells in primary culture [20].
• Unexpectedly, MBP hydrolyzed lysyl-bradykinin and methionyl-lysyl-bradykinin at the carboxyl side of Gly fairly specifically and efficiently displaying a unique cleavage [21].

Gene context of KALLIDIN

• Porcine pancreatic kallikrein applied in catalytic amounts split the kininogen molecule (apparent mass 68 kDa) with the release of lysyl-bradykinin (1 kDa) [22].
• TK has been identified as the major kininogenase of the airway and cleaves both high- and low-molecular weight kininogen to yield lysyl-bradykinin [23].
• Degradation of lysylbradykinin by endopeptidase 24.11 and endopeptidase 24.15 [24].
• These results suggest that in case of inflammation the kininogens play two physiologically distinct roles by interaction with calpains: to release lysyl-bradykinin and to inhibit proteinase activity of calpains derived from the damaged tissues [25].
• Those susceptible were somatostatin, melanocyte stimulating hormone, fibrinopeptide A, eosinophilotactictetrapeptide, lysyl-bradykinin, and methionyl-lysyl-bradykinin [26].

Analytical, diagnostic and therapeutic context of KALLIDIN

• Stimulation of basal cell/principal cell cocultures with lysylbradykinin (200 nM) evoked in principal cells a current with CFTR-Cl- channel characteristics [27].
• In four patients, the flush was concurrent with large rises (277-, 26-, 11- and 10-fold over mean basal values) in bradykinin-like immunoreactivity that was resolved by high performance liquid chromatography into lysyl-bradykinin and bradykinin (approximate ratio 1:2) [28].

References