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Reg Anesth Pain Med. 2013 Jan-Feb;38(1):9-15. doi: 10.1097/AAP.0b013e31827a3cbe.

Local anesthetic-induced inhibition of human neutrophil priming: the influence of structure, lipophilicity, and charge.

Author information

1
Department of Anesthesiology, University Hospital Maastricht, The Netherlands.

Erratum in

  • Reg Anesth Pain Med. 2013 Jul-Aug;38(4):374. Hahnenekamp, Klaus [corrected to Hahnenkamp, Klaus].

Abstract

BACKGROUND AND OBJECTIVES:

Local anesthetics (LAs) are widely known for inhibition of voltage-gated sodium channels underlying their antiarrhythmic and antinociceptive effects. However, LAs have significant immunomodulatory properties and were shown to affect human neutrophil functions independent of sodium-channel blockade. Previous studies suggest a highly selective interaction between LAs and the α-subunit of G protein-coupled receptors of the Gq/G11 family as underlying mechanism. Providing a detailed structure function analysis, this study aimed to determine the active parts within the LA molecule responsible for the effects on human neutrophil priming.

METHODS:

Human neutrophils were incubated with structurally different LAs for 60 minutes, followed by priming and activation using either platelet-activating factor or lysophosphatidic acid and N-formyl-methionyl-L-leucyl-L-phenylalanine. Superoxide anion generation was determined, using the cytochrome c reduction assay.

RESULTS:

Differences in priming inhibition of human neutrophils between LAs were smaller than expected, although significant. Ester-linked LAs blocked priming responses more effectively than did amide LAs. Furthermore, the inhibitory potency of LAs on priming decreased with an increase of their respective octanol-buffer coefficient, and inhibition did not correlate with sodium-channel-blocking potency. Charge was not crucially required for priming inhibition, yet it played a role in effect size.

CONCLUSIONS:

Local anesthetics significantly attenuated Gαq-protein-mediated neutrophil priming. The most potent inhibition was achieved by ester compounds, inversely correlated with their octanol-buffer coefficient, and enhanced by permanent charges within the LA molecule. No correlation to their potency of blocking sodium channels was found.

PMID:
23222364
DOI:
10.1097/AAP.0b013e31827a3cbe
[Indexed for MEDLINE]

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