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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Twomey, B. Muid, R. E. Dale, M. M. |
| Description | Author Affiliation: Twomey B ( Department of Pharmacology, University College London.) |
| Abstract | 1. Two compounds, reported to be potent inhibitors of protein kinase C (PKC), K252a and staurosporine, have been examined in order to gain further information as to the possible role played by PKC in the signal transduction sequence of the neutrophil respiratory burst as determined by superoxide (O2-) production. 2. A number of stimuli were used in the study, some acting at receptors i.e. fMet-Leu-Phe (fMLP), opsonized zymosan and heat-aggregated IgG (HAGG), one acting on a G-protein, fluoride, and two direct PKC activators, dioctanoylglycerol (diC8) and phorbol myristate acetate (PMA). 3. K252a and staurosporine inhibited the respiratory burst with all the stimuli but the order of agonist sensitivity was very different with the two inhibitors. 4. For K252a-induced inhibition of O2- release, the order of potency was fluoride greater than fMLP, HAGG greater than opsonized zymosan greater than PMA, DiC8. For staurosporine-induced inhibition of O2- release, the order of potency changed to fluoride greater than DiC8, PMA greater than HAGG, fMLP greater than opsonized zymosan. The significance of this unexpected difference in relative rank order of potency is discussed with reference to the reported mechanism of action of the two inhibitors and the events involved in the oxidative burst. 5. Staurosporine at low concentrations increased the fMLP-stimulated O2- response by 100%, the maximum effect occurring at 35 nM. 6. To the extent that the compounds used are specific inhibitors of PKC, these findings support a role for the enzyme PKC in stimulus-activation coupling in O2- generation with all the stimuli used in this study. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 4 |
| Volume Number | 100 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1990-08-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Alkaloids Pharmacology Carbazoles Neutrophils Metabolism Oxygen Consumption Drug Effects Protein Kinase C Antagonists & Inhibitors Dimethyl Sulfoxide In Vitro Techniques Indole Alkaloids N-Formylmethionine Leucyl-Phenylalanine Staurosporine Superoxides Tetradecanoylphorbol Acetate Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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