IngentaConnect Ca2+/Calmodulin-dependent Protein Kinase II Inhibitors Potentiate...

Authors: Watanabe M.¹; Kaihatsu T.¹; Miwa M.¹; Maeda T.¹

Source: Journal of Pharmacy and Pharmacology, Volume 51, Number 3, 1 March 1999 , pp. 295-300(6)

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Abstract:

The possible role of Ca²⁺/calmodulin-dependent protein kinase II (CaMK II) in superoxide anion (O₂^-) production induced by formyl-methionyl-leucyl-phenylalanine (FMLP) was investigated in mouse polymorphonuclear leukocytes (PMNs).

KN-93 and KN-62, specific CaMK II inhibitors, augmented FMLP-induced O₂^- production. KN-92, an analogue which did not inhibit CaMK II, did not affect O₂^- production. W-7, a calmodulin inhibitor, augmented O₂^- production when administered at 30 mM for 5 min. KN-93 and recombinant mouse tumour necrosis factor- alpha

(rmTNF-

) each augmented the maximal production of O₂^- induced by FMLP, and an additive effect of a combination of KN-93 and rmTNF- alpha

was observed. CaMK II activity in the PMNs was increased by FMLP, and the increase was inhibited by KN-93 but not by rmTNF- alpha

These results suggest that the inhibition of CaMK II resulted in the augmentation of FMLP-induced O₂^- production in PMNs by a mechanism different from that of the augmentation shown by TNF- alpha

Document Type: Research article

DOI: 10.1211/0022357991772475

Affiliations: 1: Department of Pharmaco-Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka, Japan, 422-8526

Ca2+/Calmodulin-dependent Protein Kinase II Inhibitors Potentiate Superoxide Production in Polymorphonuclear Leukocytes

Ca²⁺/Calmodulin-dependent Protein Kinase II Inhibitors Potentiate Superoxide Production in Polymorphonuclear Leukocytes