Mechanisms of non-steroid anti-inflammatory drugs action on ASICs expressed in hippocampal interneurons. J Neurochem 2008 Jul;106(1):429-41
Date
04/16/2008Pubmed ID
18410516DOI
10.1111/j.1471-4159.2008.05412.xScopus ID
2-s2.0-45249113296 (requires institutional sign-in at Scopus site) 59 CitationsAbstract
The inhibitory action of non-steroid anti-inflammatory drugs was investigated on acid-sensing ionic channels (ASIC) in isolated hippocampal interneurons and on recombinant ASICs expressed in Chinese hamster ovary (CHO) cells. Diclofenac and ibuprofen inhibited proton-induced currents in hippocampal interneurons (IC(50) were 622 +/- 34 muM and 3.42 +/- 0.50 mM, respectively). This non-competitive effect was fast and fully reversible for both drugs. Aspirin and salicylic acid at 500 muM were ineffective. Diclofenac and ibuprofen decreased the amplitude of proton-evoked currents and slowed the rates of current decay with a good correlation between these effects. Simultaneous application of acid solution and diclofenac was required for its inhibitory effect. Unlike amiloride, the action of diclofenac was voltage-independent and no competition between two drugs was found. Analysis of the action of diclofenac and ibuprofen on activation and desensitization of ASICs showed that diclofenac but not ibuprofen shifted the steady-state desensitization curve to more alkaline pH values. The reason for this shift was slowing down the recovery from desensitization of ASICs. Thus, diclofenac may serve as a neuroprotective agent during pathological conditions associated with acidification.
Author List
Dorofeeva NA, Barygin OI, Staruschenko A, Bolshakov KV, Magazanik LGMESH terms used to index this publication - Major topics in bold
Acid Sensing Ion ChannelsAcids
Animals
Anti-Inflammatory Agents, Non-Steroidal
CHO Cells
Cell Membrane
Cricetinae
Cricetulus
Cytoprotection
Diclofenac
Drug Interactions
Hippocampus
Hydrogen-Ion Concentration
Ibuprofen
Interneurons
Membrane Potentials
Nerve Tissue Proteins
Neuroprotective Agents
Organ Culture Techniques
Protons
Rats
Sodium Channels
