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)

We studied whether the components of the kallikrein-kinin system are present in the central nervous system. We found that human cerebrospinal fluid (CSF) contains free kinins: 53 +/- 15 pg/ml; kininogen: 10.9 +/- 2.1 ng kinin equivalent/ml, and kininogenase activity: 5.0 +/- 2.1 ng kinins/ml/minute. Kininogenase activity was 2-3 fold augmented by preincubation with trypsin. Soybean trypsin inhibitor completely inhibited untreated CSF and partially inhibited trypsin activated kininogenase. Kininogenase activity and immunoreactive glandular kallikrein were present in rat brain, and their concentrations in hypothalamus is several-fold higher than in cortex, pons-medulla, basal ganglia and cerebellum. In the hypophysis, activity in pars-intermedia was between 6- and 20-fold higher than in posterior and anterior hypophysis, respectively. High activity was also found in the pineal gland. The kallikrein-kinin system is present in the central nervous system where it may participate in modulation of nervous and neuroendocrine functions.
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PMID:Kallikrein-kinins in the central nervous system. 657 Jun 69

Two different plasma membrane enriched fractions were isolated from the homogenized rat kidney by differential centrifugation in dextran or sucrose. Marker enzymes and morphological studies indicated that one fraction (BLM) was enriched in membrane particles originating from the basolateral membrane of tubular cells, while the other, the PM fraction, contained membrane from the luminal side. Membrane-bound kallikrein and renin were found in both fractions. Kallikrein activity was enhanced by phospholipase A2, melittin and detergents. Renin activity was greatly increased after solubilization by the same agents. In addition to bound kallikrein and renin BLM contained a prekallikrein which was activated by trypsin or plasmin. BLM prekallikrein has a slower electrophoretic mobility and a higher molecular weight than urinary or glandular kallikrein. The basal membrane of tubular cells appears to contain all of the essential enzyme components of the kallikrein and renin systems. Kallikrein of the PM fraction is probably released into the urine, while prekallikrein and kallikrein from basal membrane may be the source of kallikrein in lymph and renal venous effluent. Membrane-bound renin could be a form of renin retained by the kidney.
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PMID:Prekallikrein, kallikrein and renin in membrane fractions of rat kidney. 675 83

The purpose of this study was to determine whether glandular kallikrein in rat pancreas is located in the beta cells of the endocrine pancreas or in the acinar cells of the exocrine pancreas. Kallikrein was measured by radial immunodiffusion and a direct radioimmunoassay in homogenates of pancreas obtained from 1) control rats, 2) rats with pancreatic beta cells selectively destroyed by streptozotocin, and 3) rats with acinar cell atrophy induced by pancreatic duct occlusion. Beta cell destruction was confirmed by the presence of hyperglycemia and by an almost total depletion of insulin-producing cells as demonstrated immunohistochemically. Acinar cell atrophy was confirmed histologically and by an almost total depletion of trypsin-like enzymes in pancreatic homogenates. The concentration of kallikrein in pancreatic homogenates was unchanged after beta cell destruction, whereas it was greatly decreased following acinar cell atrophy. Kallikrein was, by immunohistochemistry, demonstrated in the acinar cell only. The immunohistochemical localization of kallikrein agrees with the above results. These studies strongly indicate that kallikrein is predominantly located in the acinar cells of the exocrine pancreas.
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PMID:Kallikrein in rat pancreatic tissue after beta cell destruction or acinar cell atrophy. 679 5

The spicule venoms of Euproctis chrysorrhoea and Euproctis subflava were investigated for their capacity to hydrolyze chromogenic tripeptide substrates with selective affinities for various serine proteases. Seven substrates were assayed with affinities for trypsin and thrombin, trypsin and urokinase, serine proteases, chymotrypsin, glandular kallikrein, plasma kallikrein and plasmin. Venom material has a broad spectrum of affinities for the substrates with relative high plasma kallikrein activities. In E. chrysorrhoea venom, trypsin-like activities predominated, whereas E. subflava venom hydrolyzed, in preference, substrates with an affinity for chymotrypsin. The venoms were fractionated on Sephadex G-100, leading to three fractions, all having serine protease activity. The ratios of substrate specificities were markedly different, indicating that in both caterpillar venom preparations at least two separate serine proteases are present. In addition, in human plasma, inhibitor activity could be detected to the kallikrein activity of E. chrysorrhoea, but not of E. subflava. The trypsin-like activity was not inhibited by human plasma. These and earlier studies warrant the assumption that serine proteases, particularly kallikrein, are major factors in the elicitation of clinical symptoms observed after contact with caterpillar spicules.
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PMID:Protease activities in the spicule venom of Euproctis caterpillars. 704 29

Inhibitory activities of FUT-187 on trypsin-like serine proteases were compared using camostat mesilate (camostat), and 4-(4-guanidino benzoyloxy)-phenyl acetic acid methanesulfonate (GBPA) known as an active metabolite of camostat in the blood. Ki values of FUT-187 on the competitive inhibition mechanism were 0.097 microM for trypsin, 0.029 microM for pancreatic kallikrein, 0.61 microM for plasma kallikrein, 0.57 microM for plasmin, 2.5 microM for thrombin, 20.4 microM for factor Xa and 6.4 microM for C1r. However, FUT-187 acted as a noncompetitive inhibitor for factor XIIa and an uncompetitive inhibitor for C1s, and Ki values for these proteases were 0.021 and 0.18 microM, respectively. Ki values of camostat for these proteases were in the range of 0.037 to 96.4 microM, and those of GBPA for the above proteases except trypsin and plasma kallikrein were higher than those of FUT-187. The inhibitory activity of FUT-187 on trypsin was not reduced by the addition of the serum at 10%, whereas, that of GBPA was reduced (4.3 fold) in terms of IC50 values. The concentration of FUT-187 required to double APTT (activated partial thromboplastin time) was 1.09 microM, while GBPA, by concentrations up to 1 mM failed to double APTT. The kinin formation by glandular kallikrein in the rat plasma was inhibited by FUT-187 with IC50 value of 0.024 microM, while camostat revealed no inhibition by concentrations up to 1 microM. The complement-mediated hemolyses in the classical and alternative pathways were also inhibited by FUT-187 with IC50 values of 0.17 and 3.5 microM, respectively, the corresponding values for camostat being 350 and 150 microM, respectively. It is concluded that FUT-187 is a potent and selective inhibitor of trypsin-like serine proteases, and its inhibitory activities are stronger than those of camostat on glandular kallikrein, factor XIIa and C1s in complement pathway.
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PMID:[Inhibitory effects of sepimostat mesilate (FUT-187) on the activities of trypsin-like serine proteases in vitro]. 773 78

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

The Kunitz-type protease inhibitor domain from a recently identified homolog of the Alzheimer amyloid precursor protein (APPH KPI) was expressed in yeast, purified and characterized. Its inhibition profile towards several serine proteases was studied and compared to that of APP KPI, the Kunitz domain from the Alzheimer amyloid precursor protein. APPH KPI was shown to inhibit proteases with trypsin-like specificity with an inhibitor profile resembling that of the APP KPI domain. The KPI domains from APP and APPH inhibited trypsin (Ki = 0.02 nM), and plasma kallikrein (Ki = 86 nM) with approximal equal affinity. In comparison to APP KPI (Ki = 82 nM) the KPI domain of the homolog, APPH KPI, (Ki = 8.8 nM) was a more potent inhibitor of glandular kallikrein. APPH KPI was a less potent inhibitor of chymotrypsin than APP KPI (Ki = 78 nM as compared to Ki = 6 nM), plasmin (Ki = 81 nM as compared to 42 nM), and factor XIa (Ki = 14 nM as compared to Ki = 0.7 nM). The affinity of factor XIa for APPH KPI is sufficiently high to allow for an interaction in the blood. It is, however, well possible that the physiological protease ligand for the receptor-like APPH protein has yet to be identified.
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PMID:Expression, purification and characterization of a Kunitz-type protease inhibitor domain from human amyloid precursor protein homolog. 830 56

Kinin release from guinea pig plasma high molecular weight kininogen (HMWK) induced by various microbial and mite proteases has been demonstrated previously (Molla, A., Yamamoto, T., Akaike, T., Miyoshi, S., and Maeda, H. (1989) J. Biol. Chem. 264, 10589-10594; Maruo, K., Akaike, T., Matsumura, Y., Kohmoto, S., Inada, Y., Ono, T., Arao, T., and Maeda, H. (1991) Biochim. Biophys. Acta 1074, 62-68). In this paper, we describe the effects of various microbial and mite proteases on low molecular weight kininogen (LMWK) and HMWK from human plasma. A protease from the house dust mite Dermatophagoides farinae (Df-protease) directly liberated kinin from both LMWK and HMWK to a significant degree. The Km, kcat, and kcat/Km values for kinin generation from LMWK were 3.24 microM, 0.61 s-1, and 1.9 x 10(5) M-1 x s-1, respectively, and those for kinin generation from HMWK were 0.56 microM, 0.12 s-1, and 2.1 x 10(5) M-1 x s-1, respectively; kcat/Km values for Df-protease were comparable with that for glandular kallikrein. In contrast, microbial proteases showed only weak kinin-releasing activity from both human plasma kininogens. Four of ten different microbial proteases liberated kinin from LMWK, and only serratial 56-kDa protease released kinin from HMWK. Furthermore, Df-protease markedly inactivated the thiol protease inhibitory activity of LMWK and HMWK, whereas all microbial proteases (as well as the endogenous protease trypsin) did not affect this inhibitory activity of both kininogens from human plasma.
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PMID:Effect of microbial and mite proteases on low and high molecular weight kininogens. Generation of kinin and inactivation of thiol protease inhibitory activity. 834 56

Kallikrein was identified in the adrenal glands of the rat. The enzyme was present in active and inactive forms (n = 9), since preincubation with trypsin increased kininogenase activity from 54.8 +/- 11.8 to 230 +/- 23 pg bradykinin per milligram protein per minute. Adrenal kininogenase activity was inhibited by 91% by phenylmethylsulfonyl fluoride (2 mM), 81% by D-Phe-Phe-Arg-chloromethyl ketone (1 microM), 88% by aprotinin (1,000 KIU), and only 16% by soybean trypsin inhibitor (50 microM). Preincubation with antibodies against rat urinary kallikrein resulted in over 90% inhibition of kininogenase activity. Immunoreactive glandular kallikrein was 30.7 +/- 4.8 ng/mg protein (n = 11). The apparent molecular weight of the adrenal kininogenase on gel filtration chromatography was 33,000 +/- 500 D. Both the adrenal enzyme and the purified submandibular gland kallikrein used as a control had the same mobility on alkaline polyacrylamide gel electrophoresis. To determine whether messenger RNA (mRNA) for glandular kallikrein is present in adrenal gland RNA, we used the polymerase chain reaction employing oligonucleotide primers and glandular kallikrein 32P complementary DNA (cDNA) as a probe, which should give a cDNA fragment of 370 bp. Southern blots of the amplified products revealed a fragment of the predicted size. In conclusion, glandular kallikrein has been identified in the adrenal glands. The presence of mRNA for glandular kallikrein suggests that kallikrein is synthesized locally in this tissue. This provides an anatomic basis for possible participation of a local kallikrein-kinin pathway in the regulation of adrenal function.
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PMID:Adrenal kallikrein. 850

We attempted to identify the presence of kallikrein in human vascular tissue obtained from patients undergoing surgery. Sections of thoracic (n = 9) and abdominal aorta (n = 6), renal artery (n = 6), and saphenous vein (n = 17) were rinsed with 0.01 mol/L Tris-HCl buffer, cleaned, minced, and homogenized at 4 degrees C. The homogenates were centrifuged and supernatants were assayed for protein content and for active and total (trypsin activation) enzymatic activity on the peptide H-D-Val-Leu-Arg-paranitroanilide (S2266), a synthetic substrate for glandular kallikrein. Enzymatic activity was inhibited by aprotinin and polyclonal antibodies against human glandular kallikrein. Kallikrein was resistant to soybean trypsin inhibitor and had an optimum pH of 8.2. A significant correlation was found between the amidolytic and kininogenase activities measured on S2266 and dog kininogen, respectively (r = 0.83, P < .01). The kallikrein-like enzyme was present mainly in the inactive form. Higher levels were found in the homogenates of renal artery (active: 190 +/- 36, total: 5036 +/- 908 pkat/g protein) than in those of thoracic (active: 38 +/- 9, total: 973 +/- 350 pkat/g protein) and abdominal aorta (active: 44 +/- 10, total: 3031 +/- 709 pkat/g protein). In the homogenates of saphenous vein, active and total enzymatic activities averaged 188 +/- 90 and 2003 +/- 450 pkat/g protein, respectively. A significant inverse correlation was found between the levels of total enzymatic activity in saphenous vein homogenates and mean blood pressure values (r = 0.78, P < .005). These results suggest that a kallikrein-like enzyme is present in human vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A kallikrein-like enzyme in human vascular tissue. 851 58


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