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

In anesthetized and ventilated guinea pigs, intravenous injection of ET-1, ET-2, or ET-3 induced similar rapid and dose-related increases in pulmonary inflation pressure (PIP) and mean arterial blood pressure (MABP). Indomethacin inhibited the increase in PIP evoked by ET-1, ET-2, or ET-3, whereas the changes in MABP following injection of the various ET isotypes were not significantly affected. Injection of ET-1, ET-2, or ET-3 via the pulmonary artery of isolated guinea pig lungs induced similar dose-dependent increases in PIP and pulmonary perfusion pressure (PPP), thromboxane B2 (TxB2) release, and formation of lung edema. Indomethacin (5 microM), added to the perfusion medium, significantly inhibited the alterations of PIP, PPP, TxB2 release, and lung edema formation evoked by the three ET isoforms. Intravenous injection of 1 nmol/kg of big ET-1 to guinea pigs did not induce significant changes in PIP and MABP. When administered at a dose of 10 nmol/kg, big ET-1 provoked marked slow-developing and sustained increases in PIP and MABP. When big ET-1 was incubated in vitro with either alpha-chymotrypsin or pepsin and injected into guinea pigs at a dose of 1 nmol/kg, marked rapid bronchoconstrictor and pressor responses were observed. The present results demonstrate that ET-1, ET-2, and ET-3 exert comparable bronchopulmonary and pressor activities in the guinea pig. On the contrary, big ET-1 exhibits moderate direct bronchoconstrictor and pressor effects and its hydrolysis by proteases appears to be essential for expression of its full activity.
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PMID:Bronchopulmonary and pressor activities of endothelin-1 (ET-1), ET-2, ET-3, and big ET-1 in the guinea pig. 172 70

Chymase from human mast cells selectively cleaved big endothelins (ETs) at the Tyr31-Gly32 bond and produced novel trachea-constricting 31-amino acid-length endothelins, ETs(1-31), without any further degradation products. Chymases from other species, such as the enzymes from rat connective tissue and mucosal mast cells, and the other chymotrypsin-like proteases examined degraded big ETs. ETs(1-31) exhibited various contractile potencies as to the rat trachea in comparison with 21-amino acid-length endothelins, ETs(1-21), and big ETs: ET-1(1-21) > ET-1(1-31) > big ET-1; ET-2(1-31) > ET-2(1-21) > or = big ET-2; ET-3(1-21) > or = ET-3(1-31) > or = big ET-3. Among the ETs(1-31), ET-2(1-31) was the most potent constrictor, its potency being similar to that of ET-1(1-21) and stronger than that of ET-2(1-21). The contractile activity of ETs(1-31) may not be the consequence of conversion to the corresponding ETs(1-21) by phosphoramidon-sensitive ET-converting enzymes or other chymotrypsin-type proteases and metalloendopeptidases, because the contractile activity was not inhibited significantly on treatment with inhibitors of these proteases before the addition of ET-1(1-31). Inhibitors of chymotrypsin-type serine proteases, on the contrary, significantly enhanced the contractile activity exhibited by ET-1(1-31) and big ET-1, but not that by ET-1(1-21). These results suggest that protease(s) on the surface of the rat trachea tends to degrade ETs(1-31) and big ETs, and thereby reduces their contractile activity. Taken together, the results suggest that trachea-constricting ETs(1-31) generated by human chymase may play a role in the hyper-responsive airway in allergic inflammation.
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PMID:Selective conversion of big endothelins to tracheal smooth muscle-constricting 31-amino acid-length endothelins by chymase from human mast cells. 925 65