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
Jazyk angličtina Země Velká Británie, Anglie Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
18041110
DOI
10.1002/cbf.1453
Knihovny.cz E-zdroje
- MeSH
- angiotensin II farmakologie MeSH
- buněčná membrána účinky léků metabolismus MeSH
- časové faktory MeSH
- cholesterol analýza metabolismus MeSH
- hormon uvolňující thyreotropin farmakologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- proteiny vázající GTP - alfa-podjednotky Gq-G11 biosyntéza účinky léků genetika MeSH
- receptory thyroliberinu biosyntéza účinky léků MeSH
- teplota MeSH
- transfekce MeSH
- vápník metabolismus farmakologie MeSH
- vápníková signalizace účinky léků fyziologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- angiotensin II MeSH
- cholesterol MeSH
- hormon uvolňující thyreotropin MeSH
- proteiny vázající GTP - alfa-podjednotky Gq-G11 MeSH
- receptory thyroliberinu MeSH
- vápník 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
Citace poskytuje Crossref.org
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