Ca2+ responses to thyrotropin-releasing hormone and angiotensin II: the role of plasma membrane integrity and effect of G11alpha protein overexpression on homologous and heterologous desensitization
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
18041110
DOI
10.1002/cbf.1453
Knihovny.cz E-resources
- MeSH
- Angiotensin II pharmacology MeSH
- Cell Membrane drug effects metabolism MeSH
- Time Factors MeSH
- Cholesterol analysis metabolism MeSH
- Thyrotropin-Releasing Hormone pharmacology MeSH
- Cells, Cultured MeSH
- Humans MeSH
- GTP-Binding Protein alpha Subunits, Gq-G11 biosynthesis drug effects genetics MeSH
- Receptors, Thyrotropin-Releasing Hormone biosynthesis drug effects MeSH
- Temperature MeSH
- Transfection MeSH
- Calcium metabolism pharmacology MeSH
- Calcium Signaling drug effects physiology MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Angiotensin II MeSH
- Cholesterol MeSH
- Thyrotropin-Releasing Hormone MeSH
- GTP-Binding Protein alpha Subunits, Gq-G11 MeSH
- Receptors, Thyrotropin-Releasing Hormone MeSH
- Calcium MeSH
The molecular mechanisms involved in GPCR-initiated signaling cascades where the two receptors share the same signaling cascade, such as thyrotropin-releasing hormone (TRH) and angiotensin II (ANG II), are still far from being understood. Here, we analyzed hormone-induced Ca(2+) responses and the process of desensitization in HEK-293 cells, which express endogenous ANG II receptors. These cells were transfected to express exogenously high levels of TRH receptors (clone E2) or both TRH receptors and G(11)alpha protein (clone E2M11). We observed that the characteristics of the Ca(2+) response, as well as the process of desensitization, were both strongly dependent on receptor number and G(11)alpha protein level. Whereas treatment of E2 cells with TRH or ANG II led to significant desensitization of the Ca(2+) response to subsequent addition of either hormone, the response was not desensitized in E2M11 cells expressing high levels of G(11)alpha. In addition, stimulation of both cell lines with THR elicited a clear heterologous desensitization to subsequent stimulation with ANG II. On the other hand, ANG II did not affect a subsequent response to TRH. ANG II-mediated signal transduction was strongly dependent on plasma membrane integrity modified by cholesterol depletion, but signaling through TRH receptors was altered only slightly under these conditions. It may be concluded that the level of expression of G-protein-coupled receptors and their cognate G-proteins strongly influences not only the magnitude of the Ca(2+) response but also the process of desensitization and resistance to subsequent hormone addition.
Cell Biochem Funct. 2008 Mar-Apr;26(2). doi: 10.1002/cbf.1466 PubMed
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Biochemical and physiological insights into TRH receptor-mediated signaling
