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Binding and receptor down-regulation of a novel vasoconstrictor endothelin in cultured rat vascular smooth muscle cells


Binding and receptor down-regulation of a novel vasoconstrictor endothelin in cultured rat vascular smooth muscle cells



Febs Letters 239(1): 13-17



ISSN/ISBN: 0014-5793

PMID: 2846347

DOI: 10.1016/0014-5793(88)80536-2

Binding of a novel endothelium-derived vasoconstrictor endothelin (ET) and the regulation of its receptor were studied in cultured rat vascular smooth muscle cells. 125I-labeled-ET bound to the cells was resistant to acid extraction and the majority of the acid-resistant compartment was extractable with chloroform/methanol with minimal degradation. Autoradiographic studies using electron microscopy revealed that the grains were predominantly localized in the plasma membranes, but some were adjacent to and within the lysosome. Pretreatment with ET resulted in a substantial reduction of ET receptor number without changing its binding affinity. ET-induced increase in cytosolic free Ca2+ levels [( Ca2+]i] was absent or attenuated in the ET-pretreated cells. These data suggest that tight association of ET with its receptor is due to a strong interaction of its hydrophobic domain with the membrane lipids and/or its internalization within cells and that down-regulation of ET receptor is functionally linked to decreased ET-induced [Ca2+]i response.

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Accession: 039387955

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