Pepsin, an aspartic protease, converts porcine big endothelin to 21-residue endothelin.
Porcine big endothelin (big ET-39) at 1 nM, a concentration with no influence on contractile activity in isolated rat aorta, induced a slow-onset and sustained contraction by the pre-incubation with pepsin. When the incubation mixture of big ET-39 with pepsin was analyzed by high-performance liquid chromatography on an octadecyl silica column, two major products of pepsin hydrolysis were obtained; their amino acid sequences were identical with those of 21-residue endothelin (ET-21) and a C-terminal peptide of big ET-39, big ET (22-39), respectively. On the other hand, no degradation of ET-21 was observed by pepsin treatment. These results indicate that pepsin specifically cleaves a Trp21-Val22 bond in the big ET-39 molecule, producing ET-21 and big ET (22-39). Thus, the possibility that pepsin-like aspartic protease may participate in the conversion of big ET-39 to ET-21 in vivo warrants further attention.
Takaoka
M
M
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Takenobu
Y
Y
Miyata
Y
Y
Ikegawa
R
R
Matsumura
Y
Y
Morimoto
S
S
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D016232:Endothelins; D004730:Endothelium, Vascular; D006868:Hydrolysis; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010434:Pepsin A / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects
D016232:Endothelins; D010455:Peptides; D010434:Pepsin A