Origin and content of methionyl-lysyl-bradykinin, lysyl-bradykinin and bradykinin in human urine

Hial, Valdemar; Keiser, Harry R.; Pisano, John J.

doi:10.1016/0006-2952(76)90456-1

Cited by 63 publications

(22 citation statements)

References 16 publications

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“…The failure to detect methionyllyslbradykinin in the present studies was not particularly surprising. This peptide has, to date, only been detected in acidified plasma (25) or urine (26) and is probably not normally present in vivo.…”

Section: Discussionmentioning

confidence: 98%

Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen.

Proud¹,

Togias²,

Naclerio³

et al. 1983

J. Clin. Invest.

315

147

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A B S T R A C T Using a recently developed model of nasal challenge, we have obtained data that clearly demonstrate, for the first time, kinin generation during a local allergic reaction in vivo. Allergic individuals (n = 8) and matched nonallergic controls (n = 8) were challenged intranasally with the appropriate antigen and nasal washes were taken before and after challenge. Washes were assayed for kinin, histamine, and [3H]-Na-tosyl-L-arginine methyl ester (TAME)-esterase activity. Increased kinin generation was found by radioimmunoassay (RIA) in the nasal washes of all the allergics (5,560±1,670 pg/ml) but in none of the controls (38±16 pg/ml). The presence of kinin was highly correlated with that of histamine and TAME-esterase activity and with the onset of clinical symptoms (P < 0.001). Serial dilutions of nasal washes produced RIA displacement curves that paralleled the standard curve, and recovery of standard kinins that were added to nasal washes was 100±4% (n = 14). Kinin recovery was identical in both allergics and controls and did not vary significantly with antigen challenge. The immunoreactive kinin in nasal washes was stable to boiling and not precipitated by ethanol, but completely destroyed by carboxypeptidase B. It was evenly distributed between the sol and gel phases of nasal washes. High performance liquid chromatography analysis of the immunoreactive kinin in nasal washes showed it to be a mixture of lysylbradykinin and bradykinin. We conclude that kinins are produced during local allergic reactions in the nose and may contribute to the symptomatology of the allergic response.

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Section: Discussionmentioning

confidence: 98%

Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen.

Proud¹,

Togias²,

Naclerio³

et al. 1983

J. Clin. Invest.

315

147

View full text Add to dashboard Cite

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“…MKD is a rather rare kinin, confi rmed, for example, to occur in human urine (Hial et al , 1976 ) and to be formed from kininogens by human renal acid proteinase (Gomes et al , 1997 ), from LK by a mixture of elastase and plasma kallikrein (Sato and Nagasawa , 1988 ) or from HK by a combination of the neutrophil proteinase-3 and angiotensin converting enzyme (Gera et al , 2011 ). Albeit assumed to have proinfl ammatory properties comparable to those of BK and KD, this peptide has not been satisfactorily characterized as an agonist of kinin receptors.…”

Section: Discussionmentioning

confidence: 99%

Extracellular aspartic protease SAP2 of Candida albicans yeast cleaves human kininogens and releases proinflammatory peptides, Met-Lys-bradykinin and des-Arg⁹-Met-Lys-bradykinin

Bras

Bocheńska

Rapała‐Kozik

et al. 2012

Biological Chemistry

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Bradykinin-related peptides, universal mediators of infl ammation collectively referred to as the kinins, are often produced in excessive amounts during microbial infections. We have recently shown that the yeast Candida albicans , the major fungal pathogen to humans, can exploit two mechanisms to enhance kinin levels at the sites of candidial infection, one depending on adsorption and activation of the endogenous kinin-generating system of the host on the fungal cell wall and the other relying on cleavage of kinin precursors, the kininogens, by pathogen-secreted proteases. This work aimed at assigning this kininogenase activity to the major secreted aspartic protease of C. albicans (SAP2). The purifi ed SAP2 was shown to cleave human kininogens, preferably the low molecular mass form (LK) and optimally in an acidic environment (pH 3.5 -4.0), and to produce two kinins, Met-Lys-bradykinin and its derivative, [Hydroxyproline 3 ]-Met-Lys-bradykinin, both of which are capable of interacting with cellular bradykinin receptors of the B2 subtype. Additionally, albeit with a lower yield, des-Arg 9 -Met-Lysbradykinin, an effective agonist of B1-subtype receptors, was released. The pathophysiological potential of these kinins and des-Arg-kinin was also proven by presenting their ability to stimulate human promonocytic cells U937 to release proinfl ammatory interleukin 1 β (IL-1 β ) and IL-6.

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“…Urine was collected in 6 N HCl to destroy kininases and in pepstatin to inhibit uropepsin, a urinary enzyme that has been shown to generate methionyl-lysyl-bradykinin in urine at pH 1 to 2 in vitro; urine, collected in pepstatin, does not contain methionyl-lysyl-bradykinin (26). Samples were stored at -20°C and were measured at the completion of each individual study.…”

Section: Methodsmentioning

confidence: 99%

The Kallikrein-Kinin System in Bartter's Syndrome and Its Response to Prostaglandin Synthetase Inhibition

Vinci¹,

Gill²,

Bowden³

et al. 1978

J. Clin. Invest.

Self Cite

120

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A B S T R A C T The kallikrein-kinin system was characterized in seven patients with Bartter's syndrome on constant metabolic regimens before, during, and after treatment with prostaglandin synthetase inhibitors. Patients with Bartter's syndrome had high values for plasma bradykinin, plasma renin activity (PRA), urinary kallikrein, urinary immunoreactive prostaglandin E excretion, and urinary aldosterone; urinary kinins were subnormal and plasma prekallikrein was normal. Treatment with indomethacin or ibuprofen which decreased urinary immunoreactive prostaglandin E excretion by 67%, decreased mean PRA (patients recumbent) from 17.3+5.3 (S.E.M.) ng/ml per h to 3.3±1.1 ng/ml per h, mean plasma bradykinini (patients recumbent) from 15.4±4.4 ng/ml to 3.9±0.9 ng/ml, mean urinary kallikrein excretion from 24.8±3.2 tosyl-arginine-methyl ester units (TU)/ day to 12.4±2.0 TU/day, but increased mean urinary kinin excretion from 3.8±1.3 ,ug/day to 8.5±2.5 ,ug/day. Plasma prekallikrein remained unchanged at 1.4 TU/ml. Thus, with prostaglandin synthetase inhibition, values for uriniary kallikrein and kinin and plasma bradykinin returned to normal pari passu with changes in PRA, in aldosterone, and in prostaglandin E. The

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Origin and content of methionyl-lysyl-bradykinin, lysyl-bradykinin and bradykinin in human urine

Cited by 63 publications

References 16 publications

Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen.

Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen.

Extracellular aspartic protease SAP2 of Candida albicans yeast cleaves human kininogens and releases proinflammatory peptides, Met-Lys-bradykinin and des-Arg⁹-Met-Lys-bradykinin

The Kallikrein-Kinin System in Bartter's Syndrome and Its Response to Prostaglandin Synthetase Inhibition

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Origin and content of methionyl-lysyl-bradykinin, lysyl-bradykinin and bradykinin in human urine

Cited by 63 publications

References 16 publications

Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen.

Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen.

Extracellular aspartic protease SAP2 of Candida albicans yeast cleaves human kininogens and releases proinflammatory peptides, Met-Lys-bradykinin and des-Arg9-Met-Lys-bradykinin

The Kallikrein-Kinin System in Bartter's Syndrome and Its Response to Prostaglandin Synthetase Inhibition

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Extracellular aspartic protease SAP2 of Candida albicans yeast cleaves human kininogens and releases proinflammatory peptides, Met-Lys-bradykinin and des-Arg⁹-Met-Lys-bradykinin