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Urokinase‐derived peptides regulate vascular smooth muscle contraction in vitro and in vivo
Author(s) -
HajYehia Abdullah,
Nassar Taher,
Sachais Bruce S.,
Kuo Alice,
Bdeir Khalil,
AlMehdi Abu Bakr,
Mazar Andrew,
Cines Douglas B.,
Higazi Abd AlRoof
Publication year - 2000
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.14.10.1411
Subject(s) - vascular smooth muscle , chemistry , contraction (grammar) , in vivo , urokinase , peptide , vasoconstriction , in vitro , intracellular , epitope , biochemistry , microbiology and biotechnology , biology , smooth muscle , medicine , endocrinology , immunology , antigen
We examined the effect of urokinase (uPA) and its fragments on vascular smooth muscle cell contraction. Single‐chain uPA inhibits phenylepherine (PE) ‐induced contraction of rat aortic rings, whereas two‐chain uPA exerts the opposite effect. Two independent epitopes mediating these opposing activities were identified. Å6, a capped peptide corresponding to amino acids 136‐143 (KPSSPPEE) of uPA, increased the EC 50 of PE‐induced vascular contraction sevenfold by inhibiting the release of calcium from intracellular stores. Å6 activity was abolished by deleting the carboxyl‐terminal Glu or by mutating the Ser corresponding to position 138 in uPA to Glu. A single‐chain uPA variant lacking amino acids 136‐143 did not induce vasorelaxation. A second epitope within the kringle of uPA potentiated PE‐induced vasoconstriction. This epitope was exposed when single‐chain uPA was converted to a two‐chain molecule by plasmin. The isolated uPA kringle augmented vasoconstriction, whereas uPA variant lacking the kringle had no procontractile activity. These studies reveal previously undescribed vasoactive domains within urokinase and its naturally derived fragments.—Haj‐Yehia, A., Nassar, T., Sachais, B. S., Kuo, A., Bdeir, K., Al‐Mehdi, A. B., Mazar, A., Cines, D. B., Higazi, A. A. Urokinase‐derived peptides regulate vascular smooth muscle contraction in vitro and in vivo . FASEB J. 14, 1411–1422 (2000)