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- Title
Regulation of TRPM2 channels in neutrophil granulocytes by ADP-ribose: a promising pharmacological target.
- Authors
Heiner, Inka; Radukina, Natalia; Eisfeld, Jörg; Kühn, Frank; Lückhoff, Andreas
- Abstract
TRPM2 channels play an important role in the activation process of neutrophil granulocytes. One mechanism of TRPM2 channel gating is the binding of intracellular ADP ribose (ADPR) to the Nudix box domain in the C-terminal tail of TRPM2. Intracellular Ca2+, although not an activator of TRPM2 by its own, significantly enhances TRPM2 gating by ADPR. Stimulation of neutrophil granulocytes with the chemoattractant peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) induces release of Ca2+ ions from intracellular stores which in cooperation with endogenous ADPR levels enable Ca2+ influx through TRPM2. Stimulation of the ectoenzyme CD38, a membrane-associated glycohydrolase with ADPR as main product, and uptake of ADPR into the cell may contribute to the effects of fMLP. Inhibition of ADPR production, of uptake and of binding to TRPM2 are all potential pharmacological principles by which a modulation of neutrophil function may become possible in future.
- Subjects
TRP channels; PHYSIOLOGICAL control systems; ADENOSINE diphosphate; NEUTROPHILS; GRANULOCYTES; EXTRACELLULAR enzymes
- Publication
Naunyn-Schmiedeberg's Archives of Pharmacology, 2005, Vol 371, Issue 4, p325
- ISSN
0028-1298
- Publication type
Article
- DOI
10.1007/s00210-005-1033-y