Kinin-forming enzymes

H.Edery and G.P.Lewis, Plasma Kinin-Forming-Enzyme Activity in Lymph after Injury, J. Physiol., Lond. 163, 48-49P (1962). 

Like-wise angiotensin II (9 or 30 rat units per mouse) failed to augment erythropoiesis in polycythemic mice (25). However, similar quantities of both renin and angiotensin II increased blood pressure when administered intravenously to normal rats and mice (Fig. lO). Neither the REF nor the incubation mixture of REF and serum produced any vasopressor action. On the contrary, a slight drop in blood pressure was observed with the REF-serum mixture. This mild vaso-depressor action of the mixt-ure of REF and serum noted in rats and the report of a kinin-forming enzyme in the light-mitochondrial fraction of rat kidneys (2) led us to test the effect of bradykinin on erythropoiesis. Intravenous injections of 2.0 and 20 ug of bradykinin triacetate evoked no demonstrable erythropoietic response in polycythemic mice (Fig. lO). This agent did, however, produce the expected drop in blood pressure of rats. 

Carvalho, I. F. and Diniz, C. R. (1966). Kinin-forming enzyme (kininogen) in homogenates of rat kidney. Bioch. Biophys. Acta 136. 

Dr. Carrara in our laboratory has begun investigation of the purification of the kinin-forming enzyme or enzymes in the polymorphonuclear leucocytes. She finds that if she chromatographs the lysate of the white cells on Sephadex G-200 she obtains at least three peaks of activity. Since this is Sephadex, we do not know whether this may be breakdown products of an original enzyme or may represent several different enzymes. We are studying this interesting observation further. 

Jasani, Katori and Lewis (1967) have examined the origin of intracellular enzymes and the enzymes of the kinin system in the synovial fluid collected from patients with rheumatoid arthritis and related diseases. The results of this investigation have a direct bearing on the question of whether the kinin system is activated in situ or whether the kinin-forming enzymes are brought from another site inside migratory cells during the inflammatory response. 

Cathepsins and Kinin-Forming and -Destroying Enzymes Lowell M. Greenbaum... 

The effect of electronegativity and angiotensin-converting enzyme inhibition on the kinin-forming capacity of polyacrylonitrile dialysis membranes. Biomaterials, 29, 1139-1146. 

Bennett, B., Booth, N.A., Ogston D. (1987) Potential interactions between complement, coagulation, fibrinolysis, kinin-forming, and other enzyme systems, in Haemostasis and Thrombosis (2nd edn), A.L. Bloom and D.P. Thomas (eds), Churchill Livingstone, New York, pp. 267-82. 

Summary. I can summarize then by saying that our laboratory has been investigating one of the cellular elements of inflammation, the polymorphonuclear leucocyte, for enzymes that form and destroy kinins. Our investigations have shown that there are several different species of kinin-forming enz3nnes (at least by... 

We determined the concentrations of kinin-forming, kinin-destroying and kininogen activities as well as lysosomal and cytoplasmic enzymes and protein in centrifuged cell-free synovial fluid, in non-centrifu-ged synovial fluid which still contained cells and in the plasma of the same patients. The cell-free samples were centrifuged before freezing immediately after collection. All samples were frozen and thawed several times and stored at -20°C so that the cells in the non-centrifuged samples were completely disrupted before the enzymes assays were made. 

However when we consider the kinin-forming, and kinin-destroying enzymes, kininogen and protein the distribution pattern is different. Their concentrations in cell-containing synovial fluid were equal to or lower than the concentrations in either cell-free fluid or in plasma. It would therefore appear that the enzymes of the kinin system were derived not from the cells but from the plasma. This view was confirmed by the finding that the pellet obtained after centrifugation of synovial fluid contained high concentrations of the intracellular enzymes, with the exception of LDH, but only very small amounts of the kinin enzymes. 

Desormeaux, Al, Moreau, M.E., Lepage, Y, Chanard, J., Adam, A. The effect of electronegativity and angiotensin-converting enzyme inhibition on the kinin-forming capacity of polyacrylonitrile dialysis membranes. Biomateiials 29, 1139-1146 (2008)... 

The kallikrein-kinin system is an enzymatic pathway giving rise to two predominant vasoactive peptides, kallidin and bradykinin. Kallikrein, the enzyme responsible for the formation of these peptides, exists in plasma and tissues. However, circulating levels of the end products, kalhdin and bradykinin, are quite low because the kalhkrein enzymes are present largely in inactive forms. In addition, the short half-life of these peptides (15 seconds) also contributes to low plasma levels. In general, the kinins produce relaxation of vascular smooth muscle and vasodilation. Bradykinin causes... 

Kinins are potent vasodilator peptides formed enzymatically by the action of enzymes known as kallikreins or kininogenases acting on protein substrates called kininogens. The kallikrein-kinin system has several features in common with the renin-angiotensin system. 

Each kinin is formed from a kininogen by the action of a different enzyme. Bradykinin is released by plasma kallikrein, lysylbradykinin by tissue kallikrein, and methionyllysylbradykinin by pepsin and pepsin-like enzymes. The three kinins have been found in plasma and urine. Bradykinin is the predominant kinin in plasma, whereas lysylbradykinin is the major urinary form. 

Another kinin, Lys-bradykinin (also known as kallidin), is produced via the action of the tissue-kallikrein enzyme on LMWK. This enzyme is found in many tissues, either in the form of a precursor requiring activation or as an active enzyme. In contrast to plasma kallikrein, which preferentially acts upon HMWK, tissue kallikrein can release kallidin from either HMWK or LMWK. Through the action of aminopeptidases, kallidin can subsequently be converted directly into bradykinin. This enzyme is present in both the plasma and on the surface of epithelial cells. 

Kinins. These hormones are small peptides that induce contraction of smooth muscles, lower blood pressure (Box 22-D), and increase vascular permeability.176 They also have a function in contact-activated blood coagulation. The most important human kinins are the nonapeptide bradykinin177178 and the related decapeptide lysine-bradykinin (Table 30-4). Other forms such as Met-Lys-bradykinin and Ile-Ser-bradykinin (T-kinin) are also known. The precursors to the kinins, the kininogens,176 are cleaved by the protease kallikrein (Fig. 12-17) or by kallikreinlike enzymes to form the kinins. Kinins are suspected of being important producers of pain in inflammatory conditions such as arthritis.1763... 

Thi ,DPhe BK [Thi ,DPhe ]-bradykinin. bradykinin-potentiating peptide teprotide. bradykinin potentiator B teprotide. BRADYKININ RECEPTOR AGONISTS act at sites recognizing members and derivatives of the bradykinin family of hormone peptides - kinins - of which bradykinin (BK) and kallidin (lysyl-bradykinin Lys-BK KD) are the main mammalian members. The bradykinin family is distinct from the tachykinin family of peptides, though both have profound hypotensive actions and contract many intestinal and other smooth muscles. Historically, it was noted that the former action was relatively slow-developing, hence the name bradykinin. Notable actions of bradykinin and kallidin are to dilate blood vessels and increase their permeability to plasma proteins, and to stimulate sensory nerve C-fibres. These actions are pro-inflammatory, and reflect the fact that the kinin-formation system is activated in inflammation, and enzymes (kallikreins) form the kinins from blood-borne or tissue precursors (kininogens) on injurious insult. 

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