Endothelin-Like Pulmonary Vasoconstrictor Peptide Release by α -thrombin

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 86; no. 23; pp. 9529 - 9533
• Main Authors: Moon, Dudley G., Horgan, Michael J., Andersen, Thomas T., Krystek, Stanley R., Fenton, John W., Malik, Asrar B.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01-12-1989; National Acad Sciences
• Subjects: alpha -thrombin; Amino acids; Aminoacids, peptides. Hormones. Neuropeptides; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Blood Pressure - drug effects; Cells, Cultured; Chromatography, Gel; Chromatography, High Pressure Liquid; Endothelins; Endothelium, Vascular - physiology; Ethers; Fundamental and applied biological sciences. Psychology; Guinea Pigs; lung; Lung - physiology; Lungs; Molecular weight; Natural satellites; Peptides - pharmacology; Perfusion; Proteins; Pulmonary artery; Pulmonary Artery - drug effects; Pulmonary Artery - physiology; Thrombin - pharmacology; Vasoconstriction; Vasoconstrictors; Endothelial cell; Endothelin; Peptides; Molecular weight determination; Enzyme; Rodentia; HPLC chromatography; Thrombin; Pulmonary artery; Vertebrata; Mammalia; Guinea pig; Hemostasis; Perfusion; Arterial pressure; Vasoconstrictor agent
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.23.9529

The endothelial cells lining the vessel wall can modulate vasomotor tone by releasing vasoactive factors, such as endothelial-derived constricting factors. We observed that α -thrombin, but not catalytically inactivated α -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 α -thrombin, a central regulatory enzyme in hemostasis.