期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：14
页码：8196-8199
DOI：10.1073/pnas.96.14.8196
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Most physiological effects of {sigma}1 receptor ligands are sensitive to pertussis toxin, suggesting a coupling with cell membrane-bound G proteins. However, the cloning of the {sigma}1 receptor has allowed the identification of an intracellular protein anchored on the endoplasmic reticulum. Here, we show, using the isolated adult guinea pig brainstem preparation, that activation of the {sigma}1 receptor results in its translocation from the cytosol to the vicinity of the cell membrane and induces a robust and rapid decrease in hypoglossal activity, which is mediated by phospholipase C. The subsequent activation of protein kinase C {beta}1 and {beta}2 isoforms and the phosphorylation of a protein of the same molecular weight as the cloned {sigma}1 receptor lead to a desensitization of the {sigma}1 motor response. Our results indicate that the intracellular {sigma}1 receptor regulates several components implicated in plasma membrane-bound signal transduction. This might be an example of a mechanism by which an intracellular receptor modulates metabotropic responses.
