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Suzuki H, Sasaki E, Nakagawa A, et al. Diclofenac, a nonsteroidal anti-inflammatory drug, is an antagonist of human TRPM3 isoforms. Pharmacol Res Perspect. 2016;4(3):e00232doi: 10.1002/prp2.232.
Suzuki, H., Sasaki, E., Nakagawa, A., Muraki, Y., Hatano, N., & Muraki, K. (2016). Diclofenac, a nonsteroidal anti-inflammatory drug, is an antagonist of human TRPM3 isoforms. Pharmacology research & perspectives, 4(3), e00232. https://doi.org/10.1002/prp2.232
Suzuki, Hiroka, et al. "Diclofenac, a nonsteroidal anti-inflammatory drug, is an antagonist of human TRPM3 isoforms." Pharmacology research & perspectives vol. 4,3 (2016): e00232. doi: https://doi.org/10.1002/prp2.232
Suzuki H, Sasaki E, Nakagawa A, Muraki Y, Hatano N, Muraki K. Diclofenac, a nonsteroidal anti-inflammatory drug, is an antagonist of human TRPM3 isoforms. Pharmacol Res Perspect. 2016 Apr 07;4(3):e00232. doi: 10.1002/prp2.232. eCollection 2016 Jun. PMID: 27433342; PMCID: PMC4876142.
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Pharmacol Res Perspect. 2016 Apr 07;4(3):e00232. doi: 10.1002/prp2.232. eCollection 2016 Jun.

Diclofenac, a nonsteroidal anti-inflammatory drug, is an antagonist of human TRPM3 isoforms.

Pharmacology research & perspectives

Hiroka Suzuki, Eiji Sasaki, Ayumi Nakagawa, Yukiko Muraki, Noriyuki Hatano, Katsuhiko Muraki

Affiliations

  1. Laboratory of Cellular Pharmacology School of Pharmacy Aichi-Gakuin University 1-100 Kusumoto Chikusa, Nagoya 464-8650 Japan.

PMID: 27433342 PMCID: PMC4876142 DOI: 10.1002/prp2.232

Abstract

The effects of diclofenac (Dic), an acetic acid derivative-type nonsteroidal anti-inflammatory drug, were examined on the function of transient receptor potential (TRP) melastatin (TRPM) 3 (TRPM3) in human embryonic kidney 293 cell-line (HEK293) cells with recombinant human TRPM3 isoforms (TRPM31325, TRPM3-3, TRPM3-9, and TRPM3-S) and in a neuroblastoma cell line human neuroblastoma IMR-32 cells (IMR-32 cells) derived from human peripheral neurons. TRPM3 responses evoked by pregnenolone sulfate (PregS) were effectively inhibited by Dic in a concentration-dependent manner in Ca(2+) measurement and electrophysiological assays. The apparent IC 50 for PregS-induced Ca(2+) response of TRPM31325, TRPM3-3, and TRPM3-9 was calculated to be 18.8, 42.5, and 7.1 μmol/L, respectively. The TRPM3-dependent Ca(2+) responses evoked by nifedipine, another TRPM3 agonist, were also significantly inhibited by Dic. In contrast, aceclofenac, an acetoxymethyl analog of Dic, had no effects on PregS-induced TRPM3 responses. Constitutive channel activity of TRPM3-S without TRPM3 agonists was substantially inhibited by Dic, ruling out the possibility of interaction of Dic against TRPM3 agonists to the channel binding sites. Moreover, Dic reversibly inhibited TRPM3 single-channel activity recorded in excised outside-out patches without affecting the channel conductance. In differentiated neuronal IMR-32 cells with endogenous TRPM3, Dic inhibited PregS-evoked Ca(2+) responses with an apparent IC 50 of 17.1 μmol/L. Taken together, our findings demonstrate that Dic inhibits human TRPM3 without interacting with the channel pore.

Keywords: Diclofenac; TRPM3; neuroblastoma; pain

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