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Endothelin converting enzyme (ECE) activity in human vascular smooth muscle
J J Maguire1, C M Johnson, J W Mockridge
1Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital.
British Journal of Pharmacology
|January 10, 1998
Summary
Researchers identified a phosphoramidon-sensitive endothelin converting enzyme (ECE) in human umbilical vein smooth muscle. This enzyme converts big endothelin peptides into active forms, primarily acting via ETA receptors for vasoconstriction.
Area of Science:
- Pharmacology
- Vascular Biology
- Biochemistry
Background:
- Endothelin peptides (ET-1, ET-2, ET-3) are potent vasoactive substances.
- Endothelin converting enzyme (ECE) plays a crucial role in ET-1 synthesis.
- The specific ECE activity and receptor subtypes in human umbilical vein smooth muscle require further characterization.
Purpose of the Study:
- To characterize the human smooth muscle endothelin converting enzyme (ECE) in the human umbilical vein.
- To investigate the endothelin receptor subtypes mediating vasoconstriction in this preparation.
- To determine the role of ECE in the conversion of big endothelin peptides.
Main Methods:
- Human umbilical vein preparations were used to assess vasoconstrictor responses to endothelin peptides.
- Autoradiography with subtype-selective radioligands identified endothelin receptor distribution.
- Inhibition studies using phosphoramidon and thiorphan evaluated ECE and neutral endopeptidase activity.
Main Results:
- Endothelin-1 (ET-1) and ET-2 potently constricted the umbilical vein, primarily through ETA receptors.
- Autoradiography confirmed a predominance of ETA receptors in the smooth muscle media.
- A phosphoramidon-sensitive ECE was identified, capable of converting big endothelin peptides to active forms.
Conclusions:
- Human umbilical vein smooth muscle expresses functional ETA receptors mediating vasoconstriction.
- A phosphoramidon-sensitive ECE is present in the smooth muscle layer, converting big endothelin peptides.
- The precise localization and physiological significance of this ECE warrant further investigation.