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

FEBS Letters - Tập 239 - Trang 13-17 - 1988
Yukio Hirata1,2, Hiroki Yoshimi2, Shigeko Takaichi2, Masashi Yanagisawa3, Tomoh Masaki3
1Second Department of Internal Medicine Tokyo Medical and Dental University Tokyo 113, Japan
2Hypertension-Endocrine Division, National Cardiovascular Center Research Institute, Suita, Osaka 565, Japan
3Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305, Japan

Tóm tắt

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.

Tài liệu tham khảo

10.1038/332411a0 Hirata Y., 1988, Biochem. Biophys. Res. Commun. 10.1083/jcb.50.1.172 10.1016/0006-291X(84)90576-X 10.1016/S0021-9258(19)86019-2 10.1016/0006-291X(85)91903-5 10.1016/S0021-9258(19)83641-4
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FEBS Letters

Tập 239

13-17

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