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 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.
Novotný
J
J
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague.
Krůsek
J
J
Drmota
T
T
Svoboda
P
P
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D013498:Suramin / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013997:Time Factors; D014162:Transfection
D002121:Calcium Channel Blockers; D007295:Inositol Phosphates; D018025:Receptors, Thyrotropin-Releasing Hormone; D004533:Egtazic Acid; D013973:Thyrotropin-Releasing Hormone; D013498:Suramin; D019284:Thapsigargin; D019204:GTP-Binding Proteins; D009543:Nifedipine; D001920:Bradykinin; D002118:Calcium