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Title

Differential effects on neutrophil activation of staurosporin and its protein kinase C-selective derivative cgp 41231

Authors
Huggler, E.
Published in European Journal of Pharmacology. 1992, vol. 227, no. 2, p. 221-224
Abstract The relative insensitivity of the chemoattractant-induced respiratory burst to non-specific kinase inhibitors, such as staurosporin, is widely considered as evidence against the involvement of protein kinase C in signal transduction by chemoattractants. In this study we compared the effect on neutrophil activation of the non-specific kinase inhibitor staurosporin with the effect of its protein kinase C-selective derivative cgp 41251. Staurosporin activates secondary granule release by itself and enhances chemoattractant-induced primary granule release; it inhibits superoxide production in response to phorbol esters at low concentrations, but superoxide production in response to chemoattractants only at considerably higher concentrations. In contrast, cgp 41251 did not interfere with granule release, but inhibited phorbol ester- and chemoattractant-induced superoxide production with similar potency. These results suggest that many of the staurosporin effects, including its low potency to inhibit chemoattractant-induced superoxide production, are due to protein kinase C-independent effects. The results obtained with cgp 41251 are compatible with a role of protein kinase C in the mediation of the chemoattractant-induced respiratory burst of human neutrophils.
Keywords Alkaloids/ pharmacologyHumansN-Formylmethionine Leucyl-Phenylalanine/pharmacologyNeutrophils/ drug effects/metabolismProtein Kinase C/ antagonists & inhibitors/metabolismRespiratory Burst/drug effectsSignal Transduction/drug effectsStaurosporineSuperoxides/metabolismTetradecanoylphorbol Acetate/pharmacology
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PMID: 1330651
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KRAUSE, Karl-Heinz et al. Differential effects on neutrophil activation of staurosporin and its protein kinase C-selective derivative cgp 41231. In: European Journal of Pharmacology, 1992, vol. 227, n° 2, p. 221-224. https://archive-ouverte.unige.ch/unige:9381

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Deposited on : 2010-07-12

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