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Bethesda, MD: American Society for Pharmacology and Experimental Therapeutics
Erscheinungsjahr
1984
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
GH3 pituitary tumor cells were labeled to isotopic equilibrium with [3H]inositol. Thyrotropin-releasing hormone (TRH), which
has been shown to stimulate inositol phospholipid metabolism in these cells, enhanced the accumulation of [3H]inositol-derived
radioactivity in the cell's acid-soluble fraction. Separation of the [3H]inositol metabolites by ion-exchange chromatography
revealed that TRH induced a rapid rise in the cellular content of [3H]inositol mono-, bis-, and trisphosphate. The latter
two metabolites accumulated in a multiphasic manner with an initial peak 5-10 sec after TRH addition. This was followed by
a short-lived decline and a secondary rise which left the metabolite levels elevated for at least 50 min. The GH3 cell [3H]inositol
monophosphate and [3H] inositol content also rose in response to TRH, but the latter accumulated with a considerably slower
time course than the phosphorylated derivatives. None of these responses could be mimicked by the calcium ionophore A23187.
Incubation of GH3 cells with TRH in the presence of lithium led to an enhanced accumulation of [3H]inositol monophosphate
and, to a lesser extent, of [3H]inositol bis- and trisphosphate. This accumulation rose in a linear fashion with time for
at least 20 min, by which point 50% of the [3H]inositol-containing phospholipids had been depleted. When lithium was added
30 min after TRH, [3H]inositol monophosphate accumulated at the same rate as was found when TRH and lithium were added together,
indicating that the TRH-induced phospholipid response in GH3 cells does not desensitize. Under normal conditions, approximately
equal amounts of the three [3H]inositol phosphates were formed within 5 sec of TRH addition. However, when TRH was added to
cells grown chronically in lithium-containing medium, or to cells incubating at a subphysiological temperature (25 degrees),
greater than 90% of the metabolites formed were the bis- or trisphosphates. This indicates that the primary event stimulated
by TRH is the breakdown by phospholipase C of phosphatidylinositol 4,5-bisphosphate and, perhaps also, of phosphatidylinositol
4-phosphate.