Pharmacological studies on the role of protein kinase C in signal transduction of human basophils.
Recent investigations have demonstrated that activation of basophils involves the activation of protein kinase C (PKC). In the present study the effects of different nonselective and selective PKC inhibitors on IgE-mediated histamine release from human basophils were investigated. While potent but nonselective inhibitors such as staurosporine exerted a dose-dependent inhibition of Fc epsilon-receptor-mediated histamine release, staurosporine derivatives with high selectivity for PKC potentiated the IgE-mediated response. The results provide evidence that the histamine release-inhibiting activity of protein kinase inhibitors is inversely correlated with their specificity for PKC. This may confirm the hypothesis that PKC exerts a negative modulatory role during the process of stimulus secretion-coupling following receptor aggregation in basophils. Moreover, investigations with phorbol esters and diacylglycerol derivatives as potent PKC activators show that direct cellular PKC activation and antigen-stimulated mediator release are not closely correlated.
Amon
U
U
Department of Dermatology, Medical University of Lübeck, FRG.
von Stebut
E
E
Dietz
K R
KR
Bauer
F W
FW
Wolff
H H
HH
D001491:Basophils / Q000276:immunology / Q000502:physiology*; D004789:Enzyme Activation; D006636:Histamine Release / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D066298:In Vitro Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D017455:Receptors, IgE / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology*
D017455:Receptors, IgE; D007073:Immunoglobulin E; D011493:Protein Kinase C