title: Potentiation of thyrotropin releasing hormone-induced inositol phospholipid metabolism and Ca2+ mobilization by cyclic AMP-increasing agents.
abstract: Thyrotropin releasing hormone (TRH) caused significant breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2) in GH3 cells, but vasoactive intestinal peptide (VIP) did not. However, VIP enhanced the TRH-induced hydrolysis of PIP2, the conversion of phosphatidylinositol 4-phosphate (PIP) to PIP2 and the accumulation of phosphatidic acid (PA). On the other hand, the tumor promoter, tetradecanoyl phorbol acetate (TPA), suppressed the TRH-induced hydrolysis of PIP2. In the membrane fraction, the addition of cAMP inhibited the PI kinase activity in a dose-dependent manner, but stimulated the PIP kinase activity. TPA did not affect the PI and PIP kinase activities at all. VIP enhanced the first spike phase of the TRH-induced increase in the intracellular Ca2+ level, while TPA inhibited such Ca2+ mobilization. These results suggested that cAMP-increasing agents enhanced inositol phospholipid metabolism and Ca2+ mobilization induced by TRH in GH3 cells but that TPA inhibited them.
authors.affiliation: Department of Pharmacology, Tokyo Metropolitan Institute of Gerontology.
authors.forename: R
authors.initials: R
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Takenawa
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004357:Drug Synergism; D007295:Inositol Phosphates / Q000378:metabolism*; D051381:Rats; D013403:Sugar Phosphates / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
chemical_list: D007295:Inositol Phosphates; D013403:Sugar Phosphates; D014660:Vasoactive Intestinal Peptide; D013973:Thyrotropin-Releasing Hormone; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium