On the signal transducing mechanisms involved in the synergistic interaction between interleukin-1 and bradykinin on prostaglandin biosynthesis in human gingival fibroblasts

Recombinant human interleukin-1β (IL-1β) and bradykinin (BK) synergistically stimulate prostaglandin E2 (PGE2) formation in human gingival fibroblasts cultured for 24 h. Neither BK or IL-1β per se, nor their combinations, caused any acute stimulation of cellular cyclic AMP accumulation. BK, but not IL-1β, caused a rapid, transient rise of intracellular Ca2+ concentration ([Ca2+]i), as assessed by recordings of fura-2 fluorescence in monolayers of prelabelled gingival fibroblasts. IL-1β did not change the effect of BK on [Ca2+]i. Ionomycin and A 23187, two calcium ionophores, synergistically potentiated the stimulatory effect of IL-1β on PGE2 formation. Three different phorbol esters known to activate protein kinase C also synergistically potentiated the action of IL-1β on PGE2 formation. Exogenously added arachidonic acid significantly enhanced the basal formation of PGE2. In IL-1β treated cells, the enhancement of PGE2 formation seen after addition of arachidonic acid, was synergistically upregulated by IL-1β. These data show that i) the synergistic interaction between IL-1β and BK on PGE2 formation is not due to an effect linked to an upregulation of cyclic AMP or [Ca2+]i; ii) the signal transducing mechanism by which BK interacts with IL-1β, however, may be linked to a BK induced stimulation of [Ca2+]i and/or protein kinase C; iii) the mechanism involved in the action of IL-1β may, at least partly, be due to enhancement of the biosynthesis of prostanoids mediated by an upregulation of cyclooxygenase activity.

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Accumulation of Cyclic AMP Elicited by Vasoactive Intestinal Peptide Is Potentiated by Noradrenaline, Histamine, Adenosine, Baclofen, Phorbol Esters, and Ouabain in Mouse Cerebral Cortical Slices: Studies on the Role of Arachidonic Acid Metabolites and Protein Kinase C

Journal of Neurochemistry ◽

10.1111/j.1471-4159.1989.tb09265.x ◽

1989 ◽

Vol 53 (6) ◽

pp. 1941-1951 ◽

Cited By ~ 22

Author(s):

Nicolas C. Schaad ◽

Michel Schorderet ◽

Pierre J. Magistretti

Keyword(s):

Arachidonic Acid ◽

Protein Kinase C ◽

Protein Kinase ◽

Cyclic Amp ◽

Phorbol Esters ◽

Kinase C ◽

Arachidonic Acid Metabolites ◽

Acid Metabolites ◽

Cortical Slices

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Regulation of oxytocin secretion by the ovine corpus luteum: effect of activators of protein kinase C

Journal of Endocrinology ◽

10.1677/joe.0.1240225 ◽

1990 ◽

Vol 124 (2) ◽

pp. 225-232 ◽

Cited By ~ 1

Author(s):

J. J. Hirst ◽

G. E. Rice ◽

G. Jenkin ◽

G. D. Thorburn

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Cyclic Amp ◽

Corpus Luteum ◽

Phospholipase C ◽

Tissue Slices ◽

Kinase C ◽

Luteal Tissue ◽

Dose Dependent ◽

Stimulation Of

ABSTRACT The effect of protein kinase C activation and dibutyryl cyclic AMP on oxytocin secretion by ovine luteal tissue slices was investigated. Several putative regulators of luteal oxytocin secretion were also examined. Oxytocin was secreted by luteal tissue slices at a basal rate of 234·4 ± 32·8 pmol/g per h (n = 24) during 60-min incubations.Activators of protein kinase C: phorbol 12,13-dibutyrate (n = 8), phorbol 12-myristate,13-acetate (n = 4) and 1,2-didecanoylglycerol (n = 5), caused a dose-dependent stimulation of oxytocin secretion in the presence of a calcium ionophore (A23187; 0·2 μmol/l). Phospholipase C (PLC; 50–250 units/l) also caused a dose-dependent stimulation of oxytocin secretion by luteal slices. Phospholipase C-stimulated oxytocin secretion was potentiated by the addition of an inhibitor of diacylglycerol kinase (R59 022; n = 4). These data suggest that the activation of protein kinase C has a role in the stimulation of luteal oxytocin secretion. The results are also consistent with the involvement of protein kinase C in PLC-stimulated oxytocin secretion. The cyclic AMP second messenger system does not appear to be involved in the control of oxytocin secretion by the corpus luteum. Journal of Endocrinology (1990) 124, 225–232

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Bombesin and platelet-derived growth factor stimulate formation of inositol phosphates and Ca2+ mobilization in Swiss 3T3 cells by different mechanisms

Biochemical Journal ◽

10.1042/bj2580177 ◽

1989 ◽

Vol 258 (1) ◽

pp. 177-185 ◽

Cited By ~ 29

Author(s):

D M Blakeley ◽

A N Corps ◽

K D Brown

Keyword(s):

Protein Kinase C ◽

Growth Factor ◽

Protein Kinase ◽

Phorbol Esters ◽

Inositol Phosphates ◽

Platelet Derived Growth Factor ◽

3T3 Cells ◽

Kinase C ◽

Swiss 3T3 ◽

Stimulation Of

Highly purified platelet-derived growth factor (PDGF) or recombinant PDGF stimulate DNA synthesis in quiescent Swiss 3T3 cells. The dose-response curves for the natural and recombinant factors were similar, with half-maximal responses at 2-3 ng/ml and maximal responses at approx. 10 ng/ml. Over this dose range, both natural and recombinant PDGF stimulated a pronounced accumulation of [3H]inositol phosphates in cells labelled for 72 h with [3H]inositol. In addition, mitogenic concentrations of PDGF stimulated the release of 45Ca2+ from cells prelabelled with the radioisotope. However, in comparison with the response to the peptide mitogens bombesin and vasopressin, a pronounced lag was evident in both the generation of inositol phosphates and the stimulation of 45Ca2+ efflux in response to PDGF. Furthermore, although the bombesin-stimulated efflux of 45Ca2+ was independent of extracellular Ca2+, the PDGF-stimulated efflux was markedly inhibited by chelation of external Ca2+ by using EGTA. Neither the stimulation of formation of inositol phosphates nor the stimulation of 45Ca2+ efflux in response to PDGF were affected by tumour-promoting phorbol esters such as 12-O-tetradecanoylphorbol 13-acetate (TPA). In contrast, TPA inhibited phosphoinositide hydrolysis and 45Ca2+ efflux stimulated by either bombesin or vasopressin. Furthermore, whereas formation of inositol phosphates in response to both vasopressin and bombesin was increased in cells in which protein kinase C had been down-modulated by prolonged exposure to phorbol esters, the response to PDGF was decreased in these cells. These results suggest that, in Swiss 3T3 cells, PDGF receptors are coupled to phosphoinositidase activation by a mechanism that does not exhibit protein kinase C-mediated negative-feedback control and which appears to be fundamentally different from the coupling mechanism utilized by the receptors for bombesin and vasopressin.

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Activation of Protein Kinase C by Phorbol Esters and Arachidonic Acid Required for the Optimal Potentiation of Glutamate Exocytosis

Journal of Neurochemistry ◽

10.1111/j.1471-4159.1992.tb08478.x ◽

1992 ◽

Vol 59 (4) ◽

pp. 1574-1577 ◽

Cited By ~ 28

Author(s):

Immaculada Herrero ◽

María Teresa Miras-Portugal ◽

José Sánchez-Prieto

Keyword(s):

Arachidonic Acid ◽

Protein Kinase C ◽

Protein Kinase ◽

Phorbol Esters ◽

Kinase C

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The Mechanism of Skin Tumor Promotion Caused by Phorbol Esters: Possible Involvement of Arachidonic Acid Cascade/Lipoxygenase, Protein Kinase C and Calcium/Calmodulin Systems

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)43084-9 ◽

1989 ◽

Vol 49 (1) ◽

pp. 1-9

Author(s):

Teruo NAKADATE

Keyword(s):

Arachidonic Acid ◽

Protein Kinase C ◽

Protein Kinase ◽

Phorbol Esters ◽

Tumor Promotion ◽

Skin Tumor ◽

Arachidonic Acid Cascade ◽

Kinase C

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Activation of ERK1/2 by protein kinase C-α in response to hydrogen peroxide-induced cell death in human gingival fibroblasts

Toxicology in Vitro ◽

10.1016/j.tiv.2009.08.007 ◽

2010 ◽

Vol 24 (1) ◽

pp. 319-326 ◽

Cited By ~ 7

Author(s):

Gloria Gutiérrez-Venegas ◽

Juan Antonio Arreguín-Cano ◽

Rita Arroyo-Cruz ◽

Mónica Villeda-Navarro ◽

José Antonio Méndez-Mejía

Keyword(s):

Hydrogen Peroxide ◽

Cell Death ◽

Protein Kinase C ◽

Protein Kinase ◽

Human Gingival Fibroblasts ◽

Gingival Fibroblasts ◽

Kinase C

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Osmotic and phorbol ester-induced activation of Na+/H+ exchange: possible role of protein phosphorylation in lymphocyte volume regulation.

The Journal of Cell Biology ◽

10.1083/jcb.101.1.269 ◽

1985 ◽

Vol 101 (1) ◽

pp. 269-276 ◽

Cited By ~ 88

Author(s):

S Grinstein ◽

S Cohen ◽

J D Goetz ◽

A Rothstein

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Phorbol Ester ◽

Time Course ◽

Phorbol Esters ◽

Underlying Mechanism ◽

Atp Depletion ◽

Sequence Of Events ◽

Kinase C ◽

Stimulation Of

The Na+/H+ antiport is stimulated by 12-O-tetradecanoylphorbol-13, acetate (TPA) and other phorbol esters in rat thymic lymphocytes. Mediation by protein kinase C is suggested by three findings: (a) 1-oleoyl-2-acetylglycerol also activated the antiport; (b) trifluoperazine, an inhibitor of protein kinase C, blocked the stimulation of Na+/H+ exchange; and (c) activation of countertransport was accompanied by increased phosphorylation of specific membrane proteins. The Na+/H+ antiport is also activated by osmotic cell shrinking. The time course, extent, and reversibility of the osmotically induced and phorbol ester-induced responses are similar. Moreover, the responses are not additive and they are equally susceptible to inhibition by trifluoperazine, N-ethylmaleimide, and ATP depletion. The extensive analogies between the TPA and osmotically induced effects suggested a common underlying mechanism, possibly activation of a protein kinase. It is conceivable that osmotic shrinkage initiates the following sequence of events: stimulation of protein kinase(s) followed by activation of the Na+/H+ antiport, resulting in cytoplasmic alkalinization. The Na+ taken up through the antiport, together with the HCO3- and Cl- accumulated in the cells as a result of the cytoplasmic alkalinization, would be followed by osmotically obliged water. This series of events could underlie the phenomenon of regulatory volume increase.

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