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

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 (TRPM3(132...

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Autores principales: Suzuki, Hiroka, Sasaki, Eiji, Nakagawa, Ayumi, Muraki, Yukiko, Hatano, Noriyuki, Muraki, Katsuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876142/
https://www.ncbi.nlm.nih.gov/pubmed/27433342
http://dx.doi.org/10.1002/prp2.232
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author Suzuki, Hiroka
Sasaki, Eiji
Nakagawa, Ayumi
Muraki, Yukiko
Hatano, Noriyuki
Muraki, Katsuhiko
author_facet Suzuki, Hiroka
Sasaki, Eiji
Nakagawa, Ayumi
Muraki, Yukiko
Hatano, Noriyuki
Muraki, Katsuhiko
author_sort Suzuki, Hiroka
collection PubMed
description 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 (TRPM3(1325), 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 TRPM3(1325), 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.
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spelling pubmed-48761422016-07-18 Diclofenac, a nonsteroidal anti‐inflammatory drug, is an antagonist of human TRPM3 isoforms Suzuki, Hiroka Sasaki, Eiji Nakagawa, Ayumi Muraki, Yukiko Hatano, Noriyuki Muraki, Katsuhiko Pharmacol Res Perspect Original Articles 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 (TRPM3(1325), 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 TRPM3(1325), 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. John Wiley and Sons Inc. 2016-04-07 /pmc/articles/PMC4876142/ /pubmed/27433342 http://dx.doi.org/10.1002/prp2.232 Text en © 2016 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Suzuki, Hiroka
Sasaki, Eiji
Nakagawa, Ayumi
Muraki, Yukiko
Hatano, Noriyuki
Muraki, Katsuhiko
Diclofenac, a nonsteroidal anti‐inflammatory drug, is an antagonist of human TRPM3 isoforms
title Diclofenac, a nonsteroidal anti‐inflammatory drug, is an antagonist of human TRPM3 isoforms
title_full Diclofenac, a nonsteroidal anti‐inflammatory drug, is an antagonist of human TRPM3 isoforms
title_fullStr Diclofenac, a nonsteroidal anti‐inflammatory drug, is an antagonist of human TRPM3 isoforms
title_full_unstemmed Diclofenac, a nonsteroidal anti‐inflammatory drug, is an antagonist of human TRPM3 isoforms
title_short Diclofenac, a nonsteroidal anti‐inflammatory drug, is an antagonist of human TRPM3 isoforms
title_sort diclofenac, a nonsteroidal anti‐inflammatory drug, is an antagonist of human trpm3 isoforms
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876142/
https://www.ncbi.nlm.nih.gov/pubmed/27433342
http://dx.doi.org/10.1002/prp2.232
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