Chymase processes big-endothelin-2 to endothelin-2-(1-31) that induces contractile responses in the isolated monkey trachea.
Purified monkey chymase cleaved the Tyr31-Gly32 bond of big-endothelin-1 and big-endothelin-2 to yield endothelin-1-(1-31) and endothelin-2-(1-31), respectively. In the isolated monkey trachea, endothelin-1-(1-31) and endothelin-2-(1-31), as well as big-endothelin-1 and big-endothelin-2, induced contractile responses. Chymostatin, which inhibits chymase, suppressed the contractile response induced by big-endothelin-2 to 16.6% but not the responses induced by big-endothelin-1, endothelin-1-(1-31) and endothelin-2-(1-31). These results suggest that the contractile response of big-endothelin-2 is predominantly dependent on the conversion of big-endothelin-2 to endothelin-2-(1-31) by chymase.
Takai
S
S
Department of Pharmacology, Osaka Medical College, Takatsuki, Japan. pha010@art.osaka-med.ac.jp
Shiota
N
N
Jin
D
D
Miyazaki
M
M
D000818:Animals; D053818:Chymases; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D066298:In Vitro Techniques; D008252:Macaca fascicularis; D009119:Muscle Contraction / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D016232:Endothelins; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; C002101:chymostatin; D012697:Serine Endopeptidases; D053818:Chymases