Blood- and skin-derived monocytes/macrophages respond to C3a but not to C3a(desArg) with a transient release of calcium via a pertussis toxin-sensitive signal transduction pathway

1997 ◽  
Vol 27 (9) ◽  
pp. 2317-2322 ◽  
Author(s):  
Jörg Zwirner ◽  
Otto Götze ◽  
Alexander Moser ◽  
Anja Sieber ◽  
Gabriele Begemann ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Pertussis Toxin ◽  
Signal Transduction Pathway ◽  
Transduction Pathway

scholarly journals Platelet-conditioned medium increases endothelial electrical resistance independently of cAMP/PKA and cGMP/PKG

2001 ◽  
Vol 281 (5) ◽  
pp. H1992-H2001 ◽  
Author(s):  
Jonathan P. Gainor ◽  
Christine A. Morton ◽  
Jared T. Roberts ◽  
Peter A. Vincent ◽  
Fred L. Minnear
Keyword(s):  
Signal Transduction ◽  
Conditioned Medium ◽  
Pertussis Toxin ◽  
Electrical Resistance ◽  
Tyrosine Kinases ◽  
Kinase Inhibitors ◽  
Pulmonary Arteries ◽  
Signal Transduction Pathway ◽  
Transduction Pathway

Platelets release a soluble factor into blood and conditioned medium (PCM) that decreases vascular endothelial permeability. The objective of this study was to determine the signal-transduction pathway that elicits this decrease in permeability. Permeability-decreasing activity of PCM was assessed by the real-time measurement of electrical resistance across cell monolayers derived from bovine pulmonary arteries and microvessels. Using a desensitization protocol with cAMP/protein kinase A (PKA)-enhancing agents and pharmacological inhibitors, we determined that the activity of PCM is independent of PKA and PKG. Genistein, an inhibitor of tyrosine kinases, prevented the increase in endothelial electrical resistance. Because lysophosphatidic acid (LPA) has been proposed to be responsible for this activity of PCM and is known to activate the Giprotein, inhibitors of the G protein pertussis toxin and of the associated phosphatidylinositol 3-kinase (PI3K) wortmannin were used. Pertussis toxin and wortmannin caused a 10- to 15-min delay in the characteristic rise in electrical resistance induced by PCM. Inhibition of phosphorylation of extracellular signal-regulated kinase with the mitogen-activated kinase kinase inhibitors PD-98059 and U-0126 did not prevent the activity of PCM. Similar findings with regard to the cAMP protocols and inhibition of Giand PI3K were obtained for 1-oleoyl-LPA. These results demonstrate that PCM increases endothelial electrical resistance in vitro via a novel, signal transduction pathway independent of cAMP/PKA and cGMP/PKG. Furthermore, PCM rapidly activates a signaling pathway involving tyrosine phosphorylation, the Giprotein, and PI3K.

Heterotrimeric G protein Giis involved in a signal transduction pathway for ATP release from erythrocytes

2004 ◽  
Vol 286 (3) ◽  
pp. H940-H945 ◽  
Author(s):  
Jeffrey J. Olearczyk ◽  
Alan H. Stephenson ◽  
Andrew J. Lonigro ◽  
Randy S. Sprague
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
G Proteins ◽  
Pertussis Toxin ◽  
Atp Release ◽  
Signal Transduction Pathway ◽  
Protein G ◽  
Transduction Pathway ◽  
Heterotrimeric G Proteins ◽  
Heterotrimeric G Protein

Erythrocytes are reported to release ATP in response to mechanical deformation and decreased oxygen tension. Previously we proposed that receptor-mediated activation of the heterotrimeric G protein Gsresulted in ATP release from erythrocytes. Here we investigate the hypothesis that activation of heterotrimeric G proteins of the Gisubtype are also involved in a signal transduction pathway for ATP release from rabbit erythrocytes. Heterotrimeric G proteins Gαi1, Gαi2, and Gαi3but not Gαowere identified in rabbit and human erythrocyte membranes. Pretreatment of rabbit erythrocytes with pertussis toxin (100 ng/ml, 2 h), which uncouples Gi/ofrom their effector proteins, inhibited deformation-induced ATP release. Incubation of rabbit and human erythrocytes with mastoparan (Mas, 10 μM) or Mas-7 (1 μM), which are compounds that directly activate Giproteins, resulted in ATP release. However, rabbit erythrocytes did not release ATP when incubated with Mas-17 (10 μM), which is an inactive Mas analog. In separate experiments, Mas (10 μM) but not Mas-17 (10 μM) increased intracellular concentrations of cAMP when incubated with rabbit erythrocytes. Importantly, Mas-induced ATP release from rabbit erythrocytes was inhibited after treatment with pertussis toxin (100 ng/ml, 2 h). These data are consistent with the hypothesis that the heterotrimeric G protein Giis a component of a signal transduction pathway for ATP release from erythrocytes.

scholarly journals Enhancement of pertussis-toxin-sensitive Na+-dependent uridine transporter activity in HL-60 granulocytes by N-formylmethionyl-leucyl-phenylalanine

1993 ◽  
Vol 294 (3) ◽  
pp. 693-697 ◽  
Author(s):  
L B Goh ◽  
J A Sokoloski ◽  
A C Sartorelli ◽  
C W Lee
Keyword(s):  
Signal Transduction ◽  
Pertussis Toxin ◽  
Signal Transduction Pathway ◽  
Fold Increase ◽  
Ionophore A23187 ◽  
Transduction Pathway ◽  
Gradual Decline ◽  
Differentiated Cells ◽  
Dependent Transport ◽  
Full Activation

N-Formyl-Met-Leu-Phe (FMLP), at concentrations as low as 5 nM, caused an increase in intracellular uridine pools in dimethyl sulphoxide (Me2SO)-differentiated HL-60 cells. Intracellular uridine pools were elevated rapidly and reached a maximum within 10 min of exposure to 10 microM FMLP, followed by a gradual decline. This enhancement by FMLP was a consequence of a 3-fold increase in the Vmax of pertussis-toxin-sensitive Na(+)-dependent uridine transport system, with no change in the apparent Km. Km values of 2.67 +/- 0.45 and 3.85 +/- 0.52 microM and Vmax. values of 0.046 +/- 0.017 and 0.125 +/- 0.020 microM/s were obtained for untreated and FMLP-treated Me2SO-differentiated cells respectively. The effect of FMLP on the Na(+)-dependent transport of uridine in Me2SO-differentiated HL-60 cells was specific, as the facilitated transport of uridine was unaffected. Furthermore, this phenomenon was not observed in undifferentiated, phorbol 12-myristate 13-acetate (PMA)-differentiated or pertussis-toxin-treated Me2SO-differentiated HL-60 cells. Removal of extracellular Ca2+ with EGTA abolished the FMLP enhancement of uridine transport in a reversible manner, suggesting the involvement of Ca2+. However, the Ca2+ ionophore A23187 only partially mimicked the effect of FMLP. Similarly, with PMA the transport was sub-optimally enhanced, but a full activation was observed in cells treated with both A23187 and PMA. These findings suggest that activation of the Na(+)-dependent uridine transporter by FMLP in Me2SO-differentiated HL-60 cells involves a pertussis-toxin-sensitive G-protein with a bifurcating signal-transduction pathway.

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