Dataset Information

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

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 ?mol/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 ?mol/L. Taken together, our findings demonstrate that Dic inhibits human TRPM3 without interacting with the channel pore.

SUBMITTER: Suzuki H

PROVIDER: S-EPMC4876142 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Suzuki Hiroka H Sasaki Eiji E Nakagawa Ayumi A Muraki Yukiko Y Hatano Noriyuki N Muraki Katsuhiko K

Pharmacology research & perspectives 20160407 3

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 ...[more]

PMID: 27433342

Similar Datasets

Project description:BackgroundLipid transfer protein (LTP), an abundant protein in fruits, vegetables, and nuts, is a common food allergen in Mediterranean areas causing diverse allergic reactions. Approximately 40% of food-related anaphylaxis induced by LTPs requires nonsteroidal anti-inflammatory drugs (NSAIDs) as a triggering cofactor.ObjectiveWe sought to better understand the determinants of NSAID-dependent and NSAID-independent LTP-induced anaphylaxis (LTP-A).MethodsSelection of patients was based on a proved clinical history of NSAID-dependent or NSAID-independent anaphylaxis to LTPs, positive skin prick test response to LTPs, and serum LTP IgE. Whole-transcriptome (RNA sequencing) analysis of blood cells from 14 patients with NSAID-related LTP-A (NSAID-LTP-A), 7 patients with LTP-A, and 13 healthy control subjects was performed to identify distinct gene expression signatures.ResultsExpression of genes regulating gastrointestinal epithelial renewal was altered in both patient sets, particularly in those with LTP-A, who also presented with gene expression profiles characteristic of an inflammatory syndrome. These included altered B-cell pathways, increased neutrophil activation markers, and increased reactive oxygen species levels. Increased expression of the IgG receptor (CD64) in patients with LTP-A was mirrored by the presence of LTP-specific IgG1 and IgG3. Conversely, patients with NSAID-LTP-A were characterized by reduced expression of IFN-γ-regulated genes and IFN-γ levels, as well as upregulated expression of adenosine receptor 3 (ADORA3) and genes related to adenosine metabolism.ConclusionsGene ontology analysis suggests disturbances in gut epithelial homeostasis in both groups with LTP-A, with potential integrity breaches in patients with LTP-A that might explain their distinct inflammatory signatures. Differential regulation in patients with LTP-A and those with NSAID-LTP-A of the IFN-γ pathway, IgG receptors, and ADORA3 might provide the pathogenic basis of their distinct responses.

Project description:Mesoporous SBA-15 silica material was prepared by the sol-gel method and functionalized with thermosensitive polyethylenimine polymers with different molecular weight (g·mol-1): 800 (SBA-15(C)-800), 1300 (SBA-15(C)-1300) and 2000 (SBA-15(C)-2000). The nonsteroidal anti-inflammatory drug (NSAID) diclofenac sodium was selected as a model drug and encapsulated into the pores of prepared supports. Materials were characterized by the combination of infrared spectroscopy (IR), atomic force microscopy (AFM), transmission electron microscopy (TEM), photon cross-correlation spectroscopy (PCCS), nitrogen adsorption/desorption analysis, thermogravimetry (TG), differential scanning calorimetry (DSC) and small-angle X-ray diffraction (SA-XRD) experiments. The drug release from prepared matrixes was realized in two model media differing in pH, namely small intestine environment/simulated body fluid (pH = 7.4) and simulated gastric fluid (pH = 2), and at different temperatures, namely normal body temperature (T = 37 °C) and inflammatory temperature (T = 42 °C). The process of drug loading into the pores of prepared materials from the diclofenac sodium salt solutions with different concentrations and subsequent quantitative determination of released drugs was analyzed by UV-VIS spectroscopy. Analysis of prepared SBA-15 materials modified with polyethylenimines in solution showed a high ability to store large amounts of the drug, up to 230 wt.%. Experimental results showed their high drug release into the solution at pH = 7.4 for both temperatures, which is related to the high solubility of diclofenac sodium in a slightly alkaline environment. At pH = 2, a difference in drug release rate was observed between both temperatures. Indeed, at a higher temperature, the release rates and the amount of released drug were 2-3 times higher than those observed at a lower temperature. Different kinetic models were used to fit the obtained drug release data to determine the drug release rate and its release mechanism. Moreover, the drug release properties of prepared compounds were compared to a commercially available medicament under the same experimental conditions.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets