Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the pig, submandibular, native pancreatic, and urinary kallikreins are the same protein, consisting of a single polypeptide chain (alpha-kallikrein). Porcine tissue kallikrein shows very extensive sequence homology with several enzymes from submandibular glands of rats and mice, tonin, nerve growth factor gamma subunit, and submandibular proteinase A, nearly as high as with human urinary or rat submandibular kallikrein. Porcine pancreatic kallikrein isolated from partial autolyzates of pancreas carries an intrachain split (beta-kallikrein). Both chains exist in a high and low molecular weight form each because of differences in their carbohydrate content and form four types of pancreatic beta-kallikrein (B, A, III, and C). One cause of the narrow specificity of tissue kallikrein is their pronounced secondary specificity for a bulky, hydrophobic amino acid residue in P2. The hydrolysis of 10 peptide esters Ac-X-ArgOMe with different amino acids in P2 by porcine pancreatic kallikrein also showed distinct individual influences, the most favorably residues being phenylalanine and leucine as they occur in bovine kininogen. In contrast, specificity constants for hydrolysis by the digestive enzyme trypsin are similar for all these compounds. A peptide with the amino acid sequence around the methionyl bond cleaved in kininogen is also hydrolyzed by pancreatic kallikrein at this bond, but with a specificity constant three orders of magnitude lower. The lack of cleavage at lysine leading to the release of kallidin instead of bradykinin is due to the inability of porcine pancreatic kallikrein to accommodate an Arg-Pro leaving group.
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PMID:Enzymology of porcine tissue kallikrein. 655 41

A sensitive and specific radioimmunoassay for human urinary kallikrein was developed, which allows tissue kallikrein determination in human urine, saliva, pancreatic juice, bile and sweat. In several body fluids a kallikrein-like antigen was found, but not in gastric juice and breast milk. According to gel filtration studies, complex formation of kallikrein with serum proteins or different molecular weight forms of kallikrein in serum and urine may be assumed. Pancreatic kallikrein secretion follows the same pattern after stimulation with secretin and cholecystokinin as trypsin and chymotrypsin in normal individuals. In chronic pancreatitis the kinetic behaviour remains unchanged with respect to the enzyme secretion, but the secretion of kallikrein is reduced to about 20%.
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PMID:Determination of kallikrein by radioimmunoassay in human body fluids. 690 40

A synthetic peptide substrate for tissue kallikreins was hydrolysed by uterus homogenates. These also released kinins when incubated with dog kininogen. By using high pressure liquid chromatography in combination with a radioimmunoassay for kinins, the peptides released were identified as bradykinin and kallidin. Plasma kallikrein and trypsin released bradykinin from dog kininogen and hog pancreas kallikrein released kallidin from this substrate. This suggests that a tissue kallikrein and also a trypsin-like enzyme or perhaps plasma kallikrein are present in rat uterus.
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PMID:Kininogenase activity in rat uterus homogenates. 692 34

1. rK10, a weak T-kininogenase isolated from the rat submandibular gland, is a protein belonging to the rat kallikrein family. In the present work, we have studied the biological effects of rK10 with respect to its ability to alter vascular resistance, either directly like rK9, i.e. another kallikrein-like protein, trypsin and thrombin, or through the release of kinins like tissue kallikrein (rK1). The direct effect was studied by its vasomotor activity on rat isolated aortic rings since this preparation was insensitive to the action of kinins. Its ability to induce altered vascular resistance through kinin-generation was investigated by blood pressure studies in whole animals. The studies were performed in comparison to rK1. 2. Unlike rK1, which induces hypotension when administered intravenously to rats (delta BP = -56 +/- 5 mmHg, 5 micrograms kg-1), rK10 did not have any effect on systemic blood pressure (delta BP = -3 +/- 1, 5 micrograms kg-1, i.v.). 3. rK10 was without effect on uncontracted aortic rings, but showed a concentration-dependent (10(-8)-10(-6) M) relaxant effect on tissue precontracted with phenylephrine (10(-6) M). After removal of endothelial cells, no relaxation was observed. The relaxant response to rK10 was transient. rK1 (with and without endothelium), bradykinin and T-kinin (with endothelium) had no effect on contracted or uncontracted aortic rings. 4. The relaxant effect of rK10 was dependent on its enzymatic activity since preincubation with aprotinin (1.02 mM) significantly reduced vasorelaxation from 74 +/- 4% to 24 +/- 3%. 5. The relaxant effect was not inhibited by the kinin antagonist Hoe 140 (10-7 M; 34 +/- 4% without,versus 30 +/- 2% with Hoe 140), but was totally inhibited by the NO-synthase inhibitor N omega.nitro-L-arginine methyl ester (L-NAME) (2.5 x 10-4 M; 27 +/- 3% without and 2 +/- 1% with L-NAME).6. These results show that rKlO has the ability to induce vascular relaxation by a specific, direct effect on endothelial cell NO-synthesis, dependent on rK1O proteolytic activity, but independent of its ability to generate kinin. This effect, or its T-kininogenase activity in blood, was not sufficient for rK1O to have an effect on peripheral vascular resistance since intravenous injections of rK1O, unlike rKl, did not induce hypotension. Thus, rKlO does not seem to play a role in blood pressure homeostasis but may have a local effect on vascular resistance.
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PMID:Kallikrein rK10-induced kinin-independent, direct activation of NO-formation and relaxation of rat isolated aortic rings. 754 21

The activation of the kallikrein-kinin system is thought to be one of the pathophysiological factors in acute pancreatitis. A radioimmunoassay for porcine, pancreatic tissue kallikrein was developed and used to measure levels in normal plasma and peritoneal fluid and in experimental, bile-induced (group A) and bile trypsin-induced (group B) acute pancreatitis in the pig. Normal porcine plasma and peritoneal fluid contained about 2.17 +/- 0.11 and 1.91 +/- 0.19 microgram/l (SEM) tissue kallikrein, respectively. In experimental, acute pancreatitis there was a rapid rise in the plasma level of tissue kallikrein, followed by a slow increase to a final value of about 150% of the normal plasma level in both groups. In the peritoneal exudate a large increase (200-fold in group A and 2,000-fold in group B) in tissue kallikrein was seen, with a maximum within about 1/3 of the survival time, followed by a slow decrease until death in group B. In group A a smaller second peak was seen at about 2/3 of the survival time. Gelfiltration of peritoneal exudates showed complexes with alpha 1-, alpha 2-macroglobulin (alpha 1 alpha 2-M), and alpha 1-proteinase inhibitor (alpha 1-PI) and a large portion of free tissue kallikrein. The complexes with alpha 1 alpha 2-M and the free tissue kallikrein were found to be enzymatically active when tested on chromogenic tripeptide substrate. The presence of large amounts of free and active tissue kallikrein in the peritoneal exudate leads us to the conclusion that tissue kallikrein may be a major cause of local release of kinins in acute pancreatitis.
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PMID:Studies on the release of tissue kallikrein in experimental pancreatitis in the pig. 800 67

DX-9065a is an orally active newly synthesized and specific inhibitor for factor Xa. We have examined the property of DX-9065a in vitro and ex vivo. DX-9065a prolonged human plasma recalcification time, APTT and PT. Its doubling concentrations for clotting times of each coagulation assay were 0.49, 0.97 and 0.52 microM, respectively. Kinetic study revealed that DX-9065a inhibited competitively human factor Xa (Ki value: 41 nM). Ki values (microM) for other human serine proteases were as follows; thrombin > 2000, trypsin 0.62, chymotrypsin > 2000, plasmin 23, t-PA 21, plasma kallikrein 2.3 and tissue kallikrein 1000. DX-9065a up to 100 microM had no effects on human platelet aggregation. After intravenous or oral administration, DX-9065a significantly prolonged APTT and PT with a dose dependent manner. These effects were well correlated with anti-Xa activity in plasma. These results suggest that DX-9065a may become an anticoagulant by means of the specific inhibition of factor Xa.
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PMID:DX-9065a, a new synthetic, potent anticoagulant and selective inhibitor for factor Xa. 802 95

Antistasin, a potent inhibitor of the blood coagulation factor Xa, is the prototype of a novel family of serine-proteinase inhibitors. We have now isolated, sequenced and characterized an antistasin-type inhibitor from the medical leech Hirudo medicinalis. Hirustasin (Hirudo antistasin) was purified to apparent homogeneity by cation-exchange and affinity chromatography. Amino acid sequencing of the 55 amino acid protein (M(r) 5866) revealed that hirustasin is the only antistasin-type protein known to consist of one domain only; 27% and 32% sequence identity was found to the first and second domains of antistasin, respectively, and a nearly exact conservation of the spacing of the ten cysteine residues. Hirustasin is the first inhibitor of tissue kallikrein identified in leeches, and is also a tight-binding inhibitor of trypsin, chymotrypsin and neutrophil cathepsin G. However, despite the high similarity to antistasin, particularly in the vicinity of the putative reactive-site peptide bond, hirustasin neither inhibits blood coagulation in vitro nor amidolytic activity of isolated factor Xa. Thus, structural elements other than the reactive site sequence significantly influence the specificity of antistasin-type proteinase inhibitors.
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PMID:Isolation and characterization of hirustasin, an antistasin-type serine-proteinase inhibitor from the medical leech Hirudo medicinalis. 811 45

It has been reported that kinins mediate part of the beneficial cardiac effects induced by treatment with angiotensin-converting enzyme inhibitors in situations such as ischemia-reperfusion injury, myocardial infarction, and cardiac hypertrophy. However, it is not known whether the heart contains an independent kallikrein-kinin system. We measured kallikrein in tissue and in the incubation medium of heart slices. Heart slices released active and total (trypsin-activatable) kallikrein into the medium (46 +/- 5 and 380 +/- 18 pg bradykinin/mg, respectively, after 1 hour and 78 +/- 6 and 654 +/- 14 pg bradykinin/mg after 2 hours, n = 7). Release was not due to tissue damage because lactate dehydrogenase, a cytosolic marker, decreased from 8.9 +/- 2.9 to 2.9 +/- 1.0 U/mg per hour. Although kallikrein was released, total tissue kallikrein in the slices did not change (423 +/- 25 pg bradykinin/mg in nonincubated slices and 370 +/- 42 pg bradykinin/mg after 2 hours, P = NS), suggesting pool replenishment. Cardiac kallikrein activity was inhibited by incubation with anti-glandular kallikrein antibodies. Pretreatment with the protein synthesis inhibitor puromycin (10 mg IP) lowered release of active kallikrein from 78 +/- 6 to 22 +/- 4 pg bradykinin/mg and total kallikrein from 654 +/- 14 to 113 +/- 9 pg bradykinin/mg (P < .001). By using reverse transcription polymerase chain reaction with kallikrein family oligonucleotide primers and a specific kallikrein probe, we found that mRNA for tissue kallikrein is present in both atrial and ventricular RNA. Kallikrein activity was also detected in primary cultures of neonatal rat atrial and ventricular cardiocytes and their incubation medium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A local kallikrein-kinin system is present in rat hearts. 820 28

Uterine homogenates of cycling and early pregnant Sprague Dawley rats and purified rat urinary kallikrein showed similar curves of displacement of 125I-kallikrein binding to a polyclonal antibody. Uterine kallikrein concentration measured by RIA was 8.7 +/- 2 SEM ng/g wet weight during the cycle (n = 6 in diestrus and metestrus) and 20.8 +/- 2 SEM (n = 7) ng/g wet weight on Day 7 of pregnancy (P7) (p < 0.001). On P7, kallikrein concentration was increased 12.4-fold in the implantation nodes, as compared to the interimplantation segments. Uterine homogenates of rats on P7, submitted to DEAE-cellulose chromatography and Sephadex gel filtration, yielded two fractions containing kallikrein immunoreactivity and kininogenase activity, with molecular masses that ranged from 120-125 kDa and 39-43 kDa, respectively. In the RIA, both fractions displayed parallelism with purified kallikrein. Enzymatic activity was expressed after activation by trypsin. It was inhibited by aprotinin, PMSF, p-amino-benzamidine, and leupeptin, but not by soybean or ovomucoid trypsin inhibitors. Kallikrein mRNA was demonstrated by reverse transcriptase/polymerase chain reaction in uteri of nonpregnant and P7 rats. These results show that rat uterus synthesizes one or more serine proteases that are immunologically and enzymatically related to tissue kallikrein in the implantation node on P7--determined both by an increment of whole uterus kallikrein content and a depletion of the interimplantation segments--suggests that kallikrein may play a role in the vasoactive changes of implantation.
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PMID:Uterine kallikrein in the early pregnant rat. 821 45

Human seminal plasma trypsin-like proteinase inhibitor (HSTPI) was separated and examined by trypsin Cellulofine affinity adsorption and Cellulofine GCL-300 gel filtration and its inhibitory action toward some arginine amidases obtained from the urine, semen, and blood of humans. HSTPI showed strong inhibitory action toward two types of human seminal plasma basic arginine amidases (BHSAA-L and -A), human seminal plasma acidic arginine amidase with affinity to lima bean trypsin inhibitor (LBTI) column (AHSAA-L), and human acrosin and thrombin. Conversely, no or little inhibition was observed toward human urinary arginine amidase-2, human high molecular weight urokinase, or human seminal plasma acidic arginine amidase with affinity to aprotinin column (AHSAA-A, tissue kallikrein). Measurement of Ki values of BHSAA-L with affinity to LBTI column toward HSTPI and LBTI revealed that the arginine amidase had a stronger affinity for LBTI than that for HSTPI. This indicates that it is the difference in Ki values that allows BHSAA-L to be separated by the LBTI affinity adsorption method from human seminal plasma containing a large amount of HSTPI.
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PMID:Human seminal plasma proteinase inhibitor: action toward some trypsin-like arginine amidases from humans. 837 82


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