Rapid breakdown of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in rat hepatocytes stimulated by vasopressin and other Ca2+-mobilizing hormones

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Abstract
Rat hepatocytes rapidly incorporate [32P]Pi into phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]; their monoester phosphate groups approach isotopic equilibrium with the cellular precursor pools within 1 h. Upon stimulation of these prelabeled cells with Ca2+ mobilizing stimuli (V1-vasopressin, angiotensin, .alpha.1-adrenergic, ATP) there is rapid fall in the labeling of PtdIns4P and PtdIns(4,5)P2. Pharmacological studies suggest that each of the 4 stimuli acts at a different population of receptors. Insulin, glucagon and prolactin do not provoke disappearance of labeled PtdIns4P and PtdIns(4,5)P2, The labeling of PtdIns4P and PtdIns(4,5)P2 in cells stimulated with vasopressin or angiotensin initially declines at a rate of 0.5-1.0% per s, reaches a minimum after 1-2 min and then returns towards the initial value. The dose-response curves for the vasopressin- and angiotensin-stimulated responses lie close to the respective receptor occupation curves, rather than at the lower hormone concentrations needed to have evoked activation of glycogen phosphorylase. Disppearance of labeled PtdIns4P and PtdIns(4,5)P2 is not observed when cells are incubated with the ionophore A23187 [calcimycin]. The hormone-stimulated polyphosphoinositide disappearance is reduced, but not abolished, in Ca2+-depleted cells. These hormonal effects are not modified by 8-bromo cGMP, cycloheximide or .delta.-hexachlorocyclohexane. The absolute rate of polyphosphoinositide breakdown in stimulated cells is similar to the rate previously reported for the disappearance of phosphatidylinositol. These changes in polyphosphoinositide labeling apparently are caused by hormonal activation of the breakdown of PtdIns(4,5)P2 (and maybe also PtdIns4P) by the action of a polyphosphoinositide phosphodiesterase. The initial simultaneous disappearance of phosphatidylinositol might be a result of its consumption for the continuing synthesis of polyphosphosinositides.