Endothelin-Converting Enzyme Activity in Vascular Smooth Muscle Preparations In Vitro
Part of the
Methods in Molecular Biology™
book series (MIMB, volume 206)
The synthesis of ET-1, by the specific cleavage of its larger precursor big ET-1, by one or more endothelin-converting enzymes (ECE) has been discussed in Chapter 7. In the human vasculature ET-1, big ET-1 and ECE-1 are localized to secretory and storage granules (1) within endothelial cells (2). ET-1 is released via the constitutive and stimulated pathways, together with big ET-1 (3), and it is possible that additional conversion of this released big ET-1 occurs on the surface of the underlying smooth muscle cells. This is predicted by the observation that big ET-1, infused into the human forearm, significantly increases plasma levels of immunoreactive ET and decreases forearm blood flow in a phosphoramidon-sensitive manner. The hemodynamic response to big ET-1 occurred too quickly for appreciable amounts of phosphoramidon to have penetrated cell membranes, suggesting that the ECE responsible for conversion of infused big ET-1 is probably an ectoenzyme. As endothelial ECE has a predominantly intracellular localization (1), expression of ECE on the surface of human smooth muscle cells may account for the rapid response to exogenous big ET-1. This is consistent with reports that, in isolated vascular preparations, removal of the endothelium does not alter responses to big ET-1 (5-8) implying the presence of a nonendothelial, presumably smooth muscle enzyme. Indeed, ECE activity has been reported in cultured vascular smooth muscle cells (9,10) and one isoform of ECE-1, ECE-1b, has been localized to the smooth muscle cell plasma membrane (11).
KeywordsFumaric Acid Human Coronary Artery Bathing Medium Penetrate Cell Membrane Human Smooth Muscle Cell
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