scholarly journals Role of Ca2+ and protein kinase C in the receptor-mediated activation of Na+/H+ exchange in isolated liver cells

1997 ◽  
Vol 325 (3) ◽  
pp. 631-636 ◽  
Author(s):  
Angeles MARTÍN-REQUERO ◽  
Francisco J. DAZA ◽  
Ofelia G. HERMIDA ◽  
Nora BUTTA ◽  
Roberto PARRILLA
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Liver Cells ◽  
Adrenergic Agonists ◽  
Vasoactive Peptides ◽  
Kinase C ◽  
Isolated Liver Cells ◽  
Isolated Liver ◽  
Intracellular Alkalinization ◽  
Vasoactive Peptide

This work aimed to study the relationship between agonist-induced changes in cytosolic free calcium levels, protein kinase C (PKC) activity and intracellular pH in isolated liver cells. We observed that, like α1-adrenergic agonists, the Ca2+-mobilizing vasoactive peptides vasopressin and angiotensin II produced an extracellular-Na+-dependent, 5-(N-ethyl-N-isopropyl)amiloride-sensitive, intracellular alkalinization, indicative of Na+/H+ antiporter activation. Blocking the agonist-induced increase in the intracellular Ca2+ concentration using the calcium chelator bis-(o-aminophenoxy)ethane-N,N,N′,N′-tetra-acetic acid (BAPTA) prevented all types of receptor-mediated intracellular alkalinization. Thus activation of the Na+/H+ exchanger by either α1-adrenergic agonists or vasoactive peptides relies on the mobilization of intracellular Ca2+. In contrast, only the α1-adrenergic-agonist-induced alkalinization was dependent on extracellular Ca2+. Even though α1-adrenergic as well as vasoactive peptide agonists stimulated protein kinase C (PKC) activity in isolated liver cells, only the α1-adrenoreceptor-mediated intracellular alkalinization was dependent on PKC. According to these observations, Ca2+-mobilizing agonists appear to activate the Na+/H+ exchanger by at least two different mechanisms: (1) the α1-adrenoreceptor-mediated activation that is dependent on extracellular Ca2+ and PKC; and (2) vasoactive-peptide-induced alkalinization that is independent of extracellular Ca2+ and PKC. The α1-adrenoreceptor-mediated, PKC-sensitive, activation of the Na+/H+ exchanger seems to be responsible for the distinct ability of these receptors to elicit the sustained stimulation of hepatic functions.

scholarly journals 3,5,3′-Tri-iodo-l-thyronine acutely regulates a protein kinase C-sensitive, Ca2+-independent, branch of the hepatic α1-adrenoreceptor signalling pathway

1998 ◽  
Vol 331 (1) ◽  
pp. 89-97 ◽  
Author(s):  
Francisco J. DAZA ◽  
Roberto PARRILLA ◽  
Angeles MARTÍN-REQUERO
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Hepatic Metabolism ◽  
Liver Cells ◽  
Signalling Pathway ◽  
Perfused Liver ◽  
Kinase C ◽  
Isolated Liver Cells ◽  
Isolated Liver ◽  
Stimulation Of

This work aimed to investigate the acute effect of the thyroid hormone 3,5,3´-tri-iodo-l-thyronine (T3) in regulating the hepatic metabolism either directly or by controlling the responsiveness to Ca2+-mobilizing agonists. We did not detect any acute metabolic effect of T3 either in perfused liver or in isolated liver cells. However, T3 exerted a powerful inhibitory effect on the α1-adrenoreceptor-mediated responses. The promptness of this T3 effect rules out that it was the result of rate changes in gene(s) transcription. T3 inhibited the α1-adrenoreceptor-mediated sustained stimulation of respiration and release of Ca2+ and H+, but not the glycogenolytic or gluconeogenic responses, in perfused liver. In isolated liver cells, T3 enhanced the α1-agonist-induced increase in cytosolic free Ca2+ and impeded the intracellular alkalinization. Since T3 also prevented the α1-adrenoreceptor-mediated activation of protein kinase C, its effects on pH seem to be the result of a lack of activation of the Na+/H+ exchanger. The failure of T3 to prevent the α1-adrenergic stimulation of gluconeogenesis despite the inhibition of protein kinase C activation indicates that the elevation of cytosolic free Ca2+ is a sufficient signal to elicit that response. T3 also impaired some of the angiotensin-II-mediated responses, but did not alter the effects of PMA on hepatic metabolism, indicating, therefore, that some postreceptor event is the target for T3 actions. The differential effect of T3 in enhancing the α1-adrenoreceptor-mediated increase in cytosolic free Ca2+ and preventing the activation of protein kinase C, provides a unique tool for further investigating the role of each branch of the signalling pathway in controlling the hepatic functions. Moreover, the low effective concentrations of T3 (⩽ 10 nM) in perturbing the α1-adrenoreceptor-mediated response suggests its physiological significance.

scholarly journals Effect of vasopressin on the regulation of protein synthesis initiation in liver cells

1988 ◽  
Vol 254 (3) ◽  
pp. 773-779 ◽  
Author(s):  
J Menaya ◽  
R Parrilla ◽  
M S Ayuso
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Liver Cells ◽  
Initiation Factor ◽  
Protein Labelling ◽  
Kinase C ◽  
Isolated Liver Cells ◽  
Wide Range ◽  
Initiation Factor 2

Vasopressin was found to be an effective inhibitor of protein labelling in isolated liver cells. Its effect shows the following distinct characteristics: (1) in contrast with alpha-adrenergic agonists, its effect is observable under a wide range of cellular Ca2+-loading conditions; (2) it is not influenced by the nutritional state of the animal. The lack of vasopressin effect on valine production, and its ability to decrease protein labelling from near-saturation concentrations of [3H]valine, indicate that the observed variations in protein labelling reflect actual changes in the rate of protein synthesis. The action of vasopressin is primarily exerted on the initiation step of protein synthesis and this effect is accompanied by a decreased activity of eukaryotic initiation factor 2. Activators of protein kinase C showed similar but not additive effects on protein synthesis, as did vasopressin. It seems plausible to conclude that protein kinase C activation may play an important regulatory role in hepatic protein synthesis as a transducer of hormonal and perhaps other type of signals.

Protein kinase C-mediated intracellular alkalinization in rat and rabbit aortic smooth muscle cells

1987 ◽  
Vol 141 (3) ◽  
pp. 503-506 ◽  
Author(s):  
N.Raju Danthuluri ◽  
Bradford C. Berk ◽  
Tommy A. Brock ◽  
Edward J. Cragoe ◽  
Richard C. Deth
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Kinase C ◽  
Intracellular Alkalinization

Phorbol esters and arginine vasopressin in vascular smooth muscle cell activation

1989 ◽  
Vol 256 (5) ◽  
pp. F875-F881 ◽  
Author(s):  
C. Caramelo ◽  
K. Okada ◽  
P. Tsai ◽  
R. W. Schrier
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Smooth Muscle Cell ◽  
Arginine Vasopressin ◽  
Cell Shape ◽  
Shape Change ◽  
Cell Shape Change ◽  
Kinase C ◽  
Intracellular Alkalinization

Vascular smooth muscle cell (VSMC) contraction is the result of several interacting mechanisms. In this study such interactions in rat aortic VSMC in culture were examined with a focus on the role of protein kinase C-mediated mechanisms. The change in shape of VSMC was used as a functional parameter representative of contraction. The protein kinase C agonist, phorbol myristate acetate (PMA), and arginine vasopressin (AVP) induced a dose-dependent, progressive change in VSMC shape. The effects of PMA differed from AVP in the delay time necessary to reach the plateau of the response and in the absence with PMA of a transient rise in cytosolic free Ca2+ [( Ca2+]i). The effect of PMA was potentiated by the Ca2+ ionophore, ionomycin, and involved a verapamil-inhibitable transmembrane Ca2+ transport system. Protein kinase C inhibition by either isoquinolin-sulfonyl-O-2-methylpiperazine or protein kinase C desensitization significantly reduced the cell shape change induced by either PMA or AVP. In the case of AVP, this inhibitory effect occurred without affecting the [Ca2+]i transient. Therefore, the [Ca2+]i transient appears to be independent of acute protein kinase C regulation, since it is apparently not affected by the absence of protein kinase C activity. Protein kinase C activation by PMA produced intracellular alkalinization that is blocked by the sodium transport antagonist, amiloride. Amiloride also blocked the cell shape change induced by PMA or AVP. The intracellular alkalinization, however, was not necessary for the cell shape change to occur. Specifically, with the use of VSMC preincubated with fetal calf serum, PMA did not induce cellular pH changes but still produced cell shape changes.

Activation of protein kinase C sensitizes the cyclic AMP signalling system of T51B rat liver cells

1989 ◽  
Vol 1 (6) ◽  
pp. 617-625 ◽  
Author(s):  
Lise H. Aasheim ◽  
Leonard P. Kleine ◽  
Douglas J. Franks
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Rat Liver ◽  
Liver Cells ◽  
Signalling System ◽  
Kinase C ◽  
Rat Liver Cells

Steatosis inhibits liver cell store-operated Ca2+ entry and reduces ER Ca2+ through a protein kinase C-dependent mechanism

2015 ◽  
Vol 466 (2) ◽  
pp. 379-390 ◽  
Author(s):  
Claire H. Wilson ◽  
Eunüs S. Ali ◽  
Nathan Scrimgeour ◽  
Alyce M. Martin ◽  
Jin Hua ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Liver Cell ◽  
Lipid Droplets ◽  
Liver Steatosis ◽  
Liver Cells ◽  
Steatotic Liver ◽  
Kinase C ◽  
Ca2 Channels ◽  
Dependent Mechanism

Ca2+ entry through SOCs (store-operated Ca2+ channels; SOCE) is substantially inhibited in steatotic liver cells through a mechanism involving protein kinase C (PKC). Inhibition of Ca2+ entry enhances the accumulation of cytoplasmic lipid droplets and may contribute to the development of liver steatosis.

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