Activation Of Phosphatidylinositol Turnover Research Articles

Modulation of thymidine incorporation by κ-opioid ligands in rat spinal cord-dorsal root ganglion co-cultures

β-Endorphin, met-enkephalin and several μ-selective opioid agonists were shown to decrease thymidine incorporation into DNA in various neural cell cultures. We now report that the κ-selective opioid agonists U50488, U69593 and MR2034 modulate [ 3H]thymidine incorporation into DNA in rat spinal cord-dorsal root ganglion co-cultures. U50488 at 10 μM increased by 60% thymidine incorporation in 6-day-old cultures. The thymidine incorporation induced by U50488 was blocked by the κ-selective antagonist nor-binaltorphimine, as well as by pertussis toxin and LiCl U50488 treatment stimulated phosphatidylinositol turnover by three-fold compared with untreated controls. These findings suggest that κ-opioid agonists modulate DNA synthesis in spinal cord-dorsal root ganglion co-cultures through a mechanism which involves pertussis toxin-sensitive GTP-binding proteins, as well as activation of phosphatidylinositol turnover.

Combined effects of adrenergic and intravenous anesthetic agents on inositol monophosphate levels in rat liver prisms.

Combined effects of adrenergic and intravenous anesthetic agents on phosphatidylinositol (PI) turnover were studied using rat liver prisms incubated with [3H]myo-inositol. Rat liver prisms responded to epinephrine, norepinephrine and phenylephrine dose-dependently with an increase in inositol monophosphate (IP1) formation but they did not respond to ephedrine. Dopamine-induced effects were seen only at concentrations as high as 10(-4) mol.l-1. The enhancement of IP1 formation induced by epinephrine was potentiated by thiamylal at concentrations of 10(-5) mol.l-1 and 10(-4) mol.l-1, remained unaffected by ketamine, fentanyl or midazolam, but was dose-dependently inhibited by droperidol. The present results from in vitro studies of liver cell metabolism suggest that alpha-adrenergic agents in combination with barbiturates may potentiate liver cell damage by activation of PI turnover and interrelated intracellular Ca++ accumulation.

Epidermal growth factor stimulates phosphatidylinositol turnover in human foreskin fibroblasts without activation of protein kinase C.

Epidermal growth factor stimulates phosphatidylinositol turnover in human foreskin fibroblasts. This is a primary cell culture with normal numbers of epidermal growth factor receptors that is stimulated to divide by epidermal growth factor. Increases are seen in the inositol phospholipids and inositol phosphates. Despite this activation of phosphatidylinositol turnover, there is no detectable activation of protein kinase C.

Ca2+-channel blockers inhibit the action of recombinant platelet-derived growth factor in vascular smooth muscle cells.

Human platelet-derived growth factor (PDGF) is mainly composed of two polypeptide chains (PDGF-AB). All three possible dimeric forms of PDGF--i.e., PDGF-AA, PDGF-BB and PDGF-AB--exist in nature. We have used two recombinant PDGF homodimers to determine the roles of each isoform in the activation of phosphatidylinositol turnover in vascular smooth muscle cells (VSMC) isolated from rat thoracic aorta, their mitogenic effect on VSMC, and their vasoconstrictor effect on intact strips of aortic vascular tissue. Three Ca2+-channel blockers, nifedipine, verapamil, and diltiazem, were used as antagonists for investigating the PDGF-dependent changes mediated by the homodimers. PDGF-BB had a greater efficacy than PDGF-AA on inositol 1,4,5-trisphosphate release, on the formation of diacylglycerol, and on Ca2+ mobilization, which was also associated with vasoconstrictor activity and effective mitogenicity. PDGF-AA, on the other hand, was more potent than PDGF-BB in stimulating protein kinase C. In all instances, the activation of the phosphatidylinositol turnover by the two homodimers was inhibited by the Ca2+-channel blockers.

Stimulation of a MR 80,000 protein phosphorylation by EGF in EGF receptor-hyperproducing human tumor cells.

NA and Ca9-22 cells derived from squamous cell carcinomas of the tongue possess a large number of epidermal growth factor (EGF) receptors (2.0 X 10(6) and 1.3 X 10(6) receptors/cell, respectively). In these cell lines, EGF stimulated receptor autophosphorylation and phosphatidylinositol (PI) turnover. Furthermore, EGF enhanced the phosphorylation of an acidic protein of Mr 80,000. Phosphorylation of this protein was also stimulated by 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a phorbol ester tumor promoter, and was mainly at serine residues. Phosphopeptide mapping using protease V8 or trypsin indicated that Mr 80,000 proteins isolated from the EGF- and TPA-treated cells were identical. The Mr 80,000 protein was present mainly in the cytosol, but it became closely associated with the membrane as a phosphorylated form upon EGF or TPA stimulation. These results suggest that the EGF-stimulated phosphorylation of the Mr 80,000 acidic phosphoprotein in EGF receptor-hyperproducing tumor cells is mediated through the activation of PI turnover and protein kinase C.

The activation of phosphatidylinositol turnover is not directly involved in the modulation of neurotransmitter release mediated by presynaptic muscarinic receptors.

In the rat cerebral cortex, the comparative effects of various muscarinic agonists on the release of [3H]dopamine ([3H]DA), [3H]acetylcholine ([3H]ACh), and [3H]5-hydroxytryptamine ([3H]5-HT) from superfused nerve endings and on phosphatidylinositol (PI) turnover were studied. Acetylcholine (ACh) was found to be the most potent among the agonists tested on all three release systems examined, and also on the activation of PI turnover. Oxotremorine and bethanechol were very weak agonists when tested as stimulators of PI turnover. However, oxotremorine was very effective as a release modulator, while bethanechol was completely ineffective. Our data suggest that the activation of PI turnover is not directly involved in the modulation of neurotransmitter release mediated by presynaptic muscarinic receptors.

Activation of phosphatidylinositol turnover by neurotensin receptors in the human colonic adenocarcinoma cell line HT29

Association of neurotensin to its receptor in HT29 cells increases the intracellular concentration of inositol phosphates. A rapid (20–30 s), transient stimulation of inositol trisphosphate (275% of the basal level) and inositol bisphosphate (420%) is first observed, followed by a slower, stable increase in inositol monophosphate (170%). Half-maximal stimulation of the three inositol phosphates was obtained with 50–100 nM neurotensin. These results indicate that neurotensin is able to regulate intracellular Ca 2+ levels in HT29 cells by using inositol trisphosphate as a second messenger.

Activation of phosphatidylinositol turnover in rat aorta by α 1-adrenergic receptor stimulation

Activation of phosphatidylinositol turnover in rat aorta by α 1-adrenergic receptor stimulation