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Protein Phosphatase Inhibitors Exert Specific and Nonspecific Effects on Calcium Influx in Thapsigargin-Treated human Neutrophils

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Abstract

C2-ceramide but not inhibitors of phosphatase types 1 and 2A (okadaic acid, calyculin A, tautomycin) blocked store-regulated Ca2+ entry induced in human neutrophils by thapsigargin. This contrasts with previous results showing that both types of compounds inhibit Ca2+ influx in fmet-leu-phe-treated cells. In present studies, phosphatase inhibitors increased the rate of secondary Ca2+ influx in a temperature-dependent manner. Their mechanism of action appeared to be independent of phosphatase inhibition since the inactive congeners, norokadaone and tetraacetyl okadaic acid, also potentiated Ca2+ influx at similar concentrations. When Ca2+ stores were predischarged by thapsigargin, okadaic acid but not norokadaone acted synergistically with fMLP to inhibit subsequent Ca2+ entry. Results suggest that blockade of Ca2+ influx in neutrophils is mediated by a phosphorylation reaction that is prolonged by phosphatase inhibitors. The requisite phosphorylation occurs in fMLP-activated cells but may be absent in cells incubated with thapsigargin.

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, University of Calgary, Canada

    Kenneth Wong

  2. Canadian Red Cross Blood Transfusion Center, Calgary, Alberta, Canada

    Kenneth Wong & Xue-Bin Li

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  1. Kenneth Wong
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  2. Xue-Bin Li
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Wong, K., Li, XB. Protein Phosphatase Inhibitors Exert Specific and Nonspecific Effects on Calcium Influx in Thapsigargin-Treated human Neutrophils. Inflammation 22, 631–642 (1998). https://doi.org/10.1023/A:1022318631686

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