Overexpression of the G protein G 11 α prevents desensitization of CA 2+ 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 G 11 α protein in high amounts were used to analyze the desensitization phenomenon of the Ca 2+ -mobilizing pathway. Quite unexpectedly, we did not observe any significant desensitization of the [Ca 2+ ] 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 [Ca 2+ ] 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 G 11 α in desensitization of the Ca 2+ -mobilizing pathway occuring after repeated or long-term exposure of target cells to TRH-receptor agonists.