Endothelin-like pulmonary vasoconstrictor peptide release by alpha-thrombin.
The endothelial cells lining the vessel wall can modulate vasomotor tone by releasing vasoactive factors, such as endothelial-derived constricting factors. We observed that alpha-thrombin, but not catalytically inactivated alpha-thrombin, mediated the release of two pulmonary vasoconstrictor peptides into the venous effluent of guinea pig lungs. These peptides elicited a slow-onset, long-lasting pulmonary vasoconstriction similar to the effect of endothelin, an endothelial-derived 21-amino acid vasoconstrictor peptide previously isolated from cells in culture. One of the isolated peptides coelutes with endothelin upon reverse-phase HPLC with an acetonitrile gradient and has a molecular weight comparable to endothelin as determined by gel-permeation HPLC. The other vasoconstrictor peptide elutes earlier than endothelin on reverse-phase HPLC and exhibits a lower molecular weight. The studies show the release of endothelin-like pulmonary vasoconstrictor peptides in the intact lung by alpha-thrombin, a central regulatory enzyme in hemostasis.
Moon
D G
DG
Department of Physiology, Albany Medical College of Union University, NY 12208.
Horgan
M J
MJ
Andersen
T T
TT
Krystek
S R
SR
Fenton
J W
JW
Malik
A B
AB
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D016232:Endothelins; D004730:Endothelium, Vascular / Q000502:physiology; D006168:Guinea Pigs; D008168:Lung / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D013917:Thrombin / Q000494:pharmacology*; D014661:Vasoconstriction
D016232:Endothelins; D010455:Peptides; D013917:Thrombin