Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In anaesthetized and ventilated guinea-pigs, i.v. injection of 1 nmol/kg big endothelin-1 (big ET-1) did not evoke significant changes in pulmonary inflation pressure (PIP) and mean arterial blood pressure (MBP), whereas injection of the same dose of endothelin-1 (ET-1) induced marked and rapid bronchoconstrictor and pressor responses. Administered at the dose of 10 nmol/kg, big ET-1 provoked significant increases in PIP and MBP, which developed slowly and were long-lasting as compared to those evoked by ET-1. When big ET-1 was incubated for 45 min at 37 degrees C with alpha-chymotrypsin (2 mU/nmol) or pepsin (1 microgram/nmol) and then injected into guinea-pigs at the dose of 1 nmol/kg, marked bronchoconstrictor and pressor responses were observed, with kinetics similar to those noted after administration of the same dose of ET-1. The magnitude of the alpha-chymotrypsin- or pepsin-treated big ET-1 responses was similar to that induced by ET-1, incubated or not with the enzymes. Injected i.v. at the dose of 5 mg/kg, 5 min before the challenge, phosphoramidon almost totally inhibited the bronchoconstrictor and pressor responses induced by 10 nmol/kg big ET-1, whereas thiorphan (5 mg/kg) partially reduced the increase in PIP and exerted a minimal effect on the changes in MBP. Administered at the dose of 20 mg/kg per os, 1 h before i.v. administration of 10 nmol/kg big ET-1, enalapril maleate and captopril did not significantly alter the bronchoconstriction and the hypertensive response evoked by the peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of a phosphoramidon-sensitive endopeptidase in the processing of big endothelin-1 in the guinea-pig. 139 24

The potent vasoconstrictor peptide endothelin-1 is proposed to arise via proteolysis of a precursor molecule, "big endothelin," at a unique cleavage site. To aid in the identification of a putative endothelin-converting enzyme, we have developed an assay that mimics the relevant cleavage reaction. The assay takes advantage of the intramolecular fluorescence energy transfer between the scissile-site tryptophan and a dansyl moiety present in the same synthetic substrate. Cleavage of the peptide chain separates the fluorophore and quencher, resulting in an increase in fluorescence. The assay has been validated using chymotrypsin as a model protease and has been employed in the identification of novel endothelin-converting enzyme activities.
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PMID:A fluorogenic assay for endothelin-converting enzyme. 180 35

Pig endothelin-1 [ET-1-(1-21)] seems to be produced via proteolytic processing between Trp-21 and Val-22 of an intermediate form consisting of 39 amino acid residues, termed big ET-1-(1-39), by a chymotrypsin-like proteinase. We examined the chymotryptic-cleavage sites of big ET-1-(1-39) by reverse-phase h.p.l.c. and sequence analysis, and found that chymotrypsin cleaved initially the Tyr-31-Gly-32 bond of big ET-1-(1-39), followed by cleavage between Trp-21 and Val-22. Furthermore, chymotrypsin hydrolysed the generated ET-1-(1-21), producing a single major product that had the same amino acid sequence as ET-1-(1-21) with a cleavage between Tyr-13 and Phe-14. The disulphide bridge between Cys-1 and Cys-15 remained intact. These results indicate that the conversion of big ET-1-(1-39) into ET-1-(1-21) catalysed by chymotrypsin requires hydrolysis of the Tyr-31-Gly-32 bond before that of the Trp-21-Val-22 bond, an event followed by cleavage between Tyr-13 and Phe-14 within the loop of ET-1-(1-21). Thus a chymotrypsin-like proteinase might be involved not only in the production but also in the degradation of ET-1-(1-21) in vivo.
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PMID:Mode of cleavage of pig big endothelin-1 by chymotrypsin. Production and degradation of mature endothelin-1. 220 5

Endothelin-1-(1-31) is a new bioactive 31-amino-acid-length peptide generated from big endothelin-1 by chymase or other chymotrypsin-type proteases with various pathophysiologic functions. In this study, we have detected the specific and monophasic binding of [125I]endothelin-1-(1-31) in porcine lung membranes. Competition studies of [125I]endothelin-1-(1-31) binding by unlabeled endothelin-1-(1-31), endothelin-1, endothelin-3, and antagonists and agonists of endothelin ET(A) and ET(B) receptors suggest that the binding protein is an endothelin ET(B) or ET(B)-like receptor rather than an endothelin ET(A) receptor in porcine lungs. Kinetic studies showed that the affinity of endothelin-1-(1-31) to its receptor was approximately one order of magnitude lower than that of endothelin-1, and that the specific binding of endothelin-1-(1-31) was about 19% of endothelin-1 binding. The binding of [125I]endothelin-1-(1-31) was extremely slow, slower even than that of endothelin-1, and nearly irreversible. This unique quasi-irreversibility may explain the slow-onset and long-lasting biologic effects of this peptide in vivo.
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PMID:Binding of a new bioactive 31-amino-acid endothelin-1 to an endothelin ET(B) or ET(B)-like receptor in porcine lungs. 1265 Aug 30

The relative role of endothelin-1 receptors, ET(A) and ET(B) blockade in acute pancreatitis (AP) remains controversial. The aim of the study was to compare the effect of nonselective ET(A/B) antagonist (LU 302872) and selective ET(A)antagonist (LU 302146) in severe taurocholate AP in rats. Male Wistar rats with AP were treated with increasing doses: 1, 5 or 10 mg/kg b.w. of antagonists i.p. at 0, 6, 12, 18 h after induction of AP. In 24 h survivors, free active trypsin (FAT) and total potential trypsin (TPT), chymotrypsin and lipase in 12,000 x g supernatants of the pancreases were assayed. The index of trypsinogen activation (% FAT/TPT) was elevated in untreated AP to 29.2 +/- 5.0 vs 5.4 +/- 0.9 in the control (p < 0.001). ET(A/B) antagonist at increasing doses, diminished this index to 9.8 +/- 2.7, 10.3 +/- 1.6 and 10.1 +/- 2.0 respectively (p < 0.005). ET(A) antagonist reduced % FAT/TPT ratio to 10.6 +/- 1.9 (p < 0.005), 13.4 +/- 0.5 (p < 0.001) and 10.2 +/- 2.4 (p < 0.005) at respective doses. Both antagonists to a similar degree reduced the histological scores of inflammation, hemorrhages and necrosis. The increase in chymotrypsin and lipase activities after 24 h was not significant. In conclusion, both nonselective ET(A/B) and selective ET(A) antagonists attenuated to similar degree the augmented trypsinogen activation and pancreatic injury in taurocholate acute experimental pancreatitis in rats. Endothelin-1 receptor antagonists could be beneficial in the course of acute pancreatitis by the attenuation of trypsinogen activation.
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PMID:The effect of endothelin-1 receptor antagonists in acute experimental pancreatitis in the rats. 1462 May 34

Injection of 1 nmol/kg Big-endothelin-1 (ET-1) into anaesthetized and ventilated guinea-pigs did not evoke significant changes in pulmonary inflation pressure and mean arterial blood pressure. In contrast, injection of 1 nmol/kg ET-1 induced marked and rapid bronchoconstrictor and pressor responses. When administered at a dose of 10 nmol/kg, Big-ET-1 induced marked long-lasting changes in pulmonary inflation pressure and mean arterial blood pressure developing slowly as compared to those evoked by ET-1. Furthermore, these increases reached maximal values by 20 min for pulmonary inflation pressure and 45 min for mean arterial blood pressure after injection of the peptide. When Big-ET-1 was incubated with ?-chymotrypsin [45 min at 37 degrees C, enzyme : substrate ratio (wt/wt) : 0.5%] and injected into guinea-pigs at a dose of 1 nmol/kg, marked bronchoconstrictor and pressor responses were observed, developing with the same kinetics as those evoked by ET-1. The extent of the pressor response was similar and the bronchoconstriction was slightly lower than those evoked upon injection of 1 nmol/kg ET-1 treated or not with ?-chymotrypsin. The present results indicate that Big-ET exhibits moderate, if any, direct bronchoconstrictor and pressor activities in the guinea-pig. The slow metabolism of Big-ET-1 in an active form probably explains its long-lasting effects at a dose of 10 nmol/kg. This is indirectly confirmed by the in vitro treatment of Big-ET-1 with ?-chymotrypsin which converts the peptide into an active form.
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PMID:Bronchopulmonary and pressor effects of big-endothelin-1 in the guinea-pig. 2050 29