Overexpression of the G protein G11alpha prevents desensitization of Ca2+ response to thyrotropin-releasing hormone

Doubly transfected human embryonal kidney cells (clone E2M11 of the HEK 293 cell line) expressing both thyrotropin-releasing hormone (TRH) receptors and G11alpha protein in high amounts were used to analyze the desensitization phenomenon of the Ca2+-mobilizing pathway. Quite unexpectedly, we did not...

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Bibliographic Details
Published in:Life sciences (1973) 1999, Vol.65 (9), p.889-900
Main Authors: Novotný, J, Krůsek, J, Drmota, T, Svoboda, P
Format: Article
Language:English
Subjects:
Animals
Bradykinin - pharmacology
Calcium - metabolism
Calcium - pharmacology
Calcium Channel Blockers - pharmacology
Calcium Signaling - drug effects
Cell Line
Dose-Response Relationship, Drug
Egtazic Acid - pharmacology
Gene Expression
GTP-Binding Proteins - antagonists & inhibitors
GTP-Binding Proteins - genetics
GTP-Binding Proteins - metabolism
Humans
Inositol Phosphates - metabolism
Nifedipine - pharmacology
Rats
Receptors, Thyrotropin-Releasing Hormone - agonists
Receptors, Thyrotropin-Releasing Hormone - antagonists & inhibitors
Receptors, Thyrotropin-Releasing Hormone - genetics
Receptors, Thyrotropin-Releasing Hormone - physiology
Suramin - pharmacology
Thapsigargin - pharmacology
Thyrotropin-Releasing Hormone - agonists
Thyrotropin-Releasing Hormone - antagonists & inhibitors
Thyrotropin-Releasing Hormone - pharmacology
Time Factors
Transfection
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Summary:Doubly transfected human embryonal kidney cells (clone E2M11 of the HEK 293 cell line) expressing both thyrotropin-releasing hormone (TRH) receptors and G11alpha protein in high amounts were used to analyze the desensitization phenomenon of the Ca2+-mobilizing pathway. Quite unexpectedly, we did not observe any significant desensitization of the [Ca2+]i response to TRH in these cells after repeated or prolonged incubation with the hormone (up to 5 h). Under the same conditions, the TRH-induced [Ca2+]i response was completely desensitized in the parent cell line (293-E2 cels) expressing TRH receptors alone. In both cell lines, inositol phosphate response was desensitized after TRH exposure, although basal levels of inositol phospates in TRH-pretreated cells were much higher than in "naive" TRH-unexposed cells. These data suggest a significant role of the G protein G11alpha in desensitization of the Ca2+-mobilizing pathway occuring after repeated or long-term exposure of target cells to TRH-receptor agonists.
ISSN:0024-3205