Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bradykinin / pharmacology
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Calcium / metabolism
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Calcium / pharmacology
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Calcium Channel Blockers / pharmacology
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Calcium Signaling / drug effects*
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Cell Line
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Dose-Response Relationship, Drug
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Egtazic Acid / pharmacology
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GTP-Binding Proteins / antagonists & inhibitors
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / metabolism*
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Gene Expression
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Humans
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Inositol Phosphates / metabolism
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Nifedipine / pharmacology
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Rats
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Receptors, Thyrotropin-Releasing Hormone / agonists
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Receptors, Thyrotropin-Releasing Hormone / antagonists & inhibitors*
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Receptors, Thyrotropin-Releasing Hormone / genetics
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Receptors, Thyrotropin-Releasing Hormone / physiology
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Suramin / pharmacology
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Thapsigargin / pharmacology
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Thyrotropin-Releasing Hormone / agonists
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Thyrotropin-Releasing Hormone / antagonists & inhibitors
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Thyrotropin-Releasing Hormone / pharmacology*
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Time Factors
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Transfection
Substances
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Calcium Channel Blockers
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Inositol Phosphates
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Receptors, Thyrotropin-Releasing Hormone
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Egtazic Acid
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Thyrotropin-Releasing Hormone
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Suramin
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Thapsigargin
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GTP-Binding Proteins
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Nifedipine
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Bradykinin
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Calcium