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Inhibition of hASIC‐1b by ibuprofen
Author(s) -
Qadri Yawar Jamal,
Fuller Catherine M,
Benos Dale J
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a955
Subject(s) - ibuprofen , acid sensing ion channel , xenopus , chemistry , pharmacology , cyclooxygenase , patch clamp , hek 293 cells , ion channel , enantiomer , heterologous expression , analgesic , biophysics , enzyme , recombinant dna , receptor , biochemistry , biology , stereochemistry , gene
Ibuprofen is a common drug that is often used for pain management. Conventionally, its actions are explained by inhibition of cyclooxygenase and the subsequent generation of prostanoids. However, it was recently noted that ibuprofen acutely inhibited rat Acid‐Sensing Ion Channel 1a (ASIC‐1a) channels ( Voilley et al. J. Neurosci. 21:8026, 2001 ). These proton gated channels are involved in many important processes including nociception. To examine this interaction, we used two‐electrode voltage clamp and patch clamp in heterologous expression systems. We have found that 0.5 mM racemic ibuprofen reduced the acid induced current to 48.5% ± 1.5% (n=3) of the expected value in Xenopus oocytes expressing human ASIC‐1b. This inhibition is not seen in TREX HEK cells expressing hASIC‐2b and hASIC‐1b, suggesting that the inhibition is specific for hASIC‐1b monomeric channels. As enantiomers of ibuprofen show differing biological activity, we intend to isolate the actions of R‐ and S‐ibuprofen. To deduce the protein domains necessary for this interaction, chimeras made by swapping domains of ibuprofen‐sensitive hASIC‐1b with ibuprofen‐insensitive hASIC‐2b will be used to map drug‐channel interaction domains. This work aims to build a pathway to better understanding of both the modulation of hASIC‐1b and the mechanisms of ibuprofen’s actions in the body. This study was supported by NIH Grant CA101952 and DK37206.