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

FEBS Letters

Takaichi, Shigeko¹  Hirata, Yukio³  Masaki, Tomoh²  Yoshimi, Hiroki¹  Yanagisawa, Masashi² 

[1] Hypertension-Endocrine Division, National Cardiovascular Center Research Institute, Suita, Osaka 565, Japan;Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305, Japan;Second Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113, Japan

关键词: Endothelin;    Receptor binding;    Receptor down-regulation;    cytosolic free Ca2+;    (Vascular smooth muscle cell);   

DOI  :  10.1016/0014-5793(88)80536-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown