Percentages of activation or inhibition in Ca2+ microfluorometry assays of TRPV1, TRPV3, TRPA1, TRPM3, and ASIC3 channels selected β-lactams (10 µM)
Compound
Config
hTRPV1 agonism (%)
hTRPV1 antagonism (%)
hTRPV3 antagonism (%)
hTRPA1 agonism (%)
hTRPA1 antagonism (%)
hTRPM3 antagonism (%)
ASIC3 antagonism (%)
1a
3S,4S,2'S
31.3 ± 3.6
19.4 ± 1.7
–6.3 ± 5.9
0.4 ± 0.3
4.2 ± 1.1
ND
6.0 ± 0.9
1b
3S,4S,2'R
4.7 ± 3.6
–9.4 ± 15.1
–6.6 ± 2.9
0.4 ± 0.2
–2.4 ± 7.5
8.9 ± 8.8
–10.1 ± 8.9
1c
3R,4R,2'S
63.7 ± 3.1
52.6 ± 17.0a
6.6 ± 2.5
0.7 ± 0.1
–13.1 ± 8.8
7.5 ± 10.3
ND
1d
3R,4R,2'R
–2.2 ± 3.2
–1.5 ± 0.8
11.2 ± 3.0
0.2 ± 0.6
–6.1 ± 4.9
8.5 ± 1.8
ND
9d
3R,4R,2'R
4.9 ± 0.6
–8.8 ± 2.9
0.1 ± 0.9
1.3 ± 0.2
7.8 ± 0.6
10.6 ± 2.9
ND
11a
3S,4S,2'S
26.7 ± 3.1
46.4 ± 0.4a
7.1 ± 0.4
1.1 ± 0.4
9.5 ± 3.4
19.9 ± 6.6
2.1 ± 6.2
hTRPV1: human transient receptor potential vanilloid, type 1; hTRPA1: human transient receptor potential ankirin, type 1; hTRPM3: human transient receptor potential melastatin, subtype 3; ASIC3: acid sensing ion cannel, subunit 3; IC50: concentration exerting a half-maximal inhibition; ND: no data. In all cases, data is from two experiments in duplicate. Agonism: assay for agonist activity. Antagonism: assay for antagonist activity (see Materials and methods). Agonists used for activation of the different channels: TRPV1 (capsaicin, 30 nM), TRPV3 [2-aminoethoxydiphenyl borate (2-APB), 30 µM], TRPA1 (allylisothiocyanate, 10 µM), TRPM3 (pregnenolone sulfate, 50 µM), ASIC3 (buffer, pH 5.5). Antagonists used as references: TRPV1 (capsazepin, IC50 1.3 × 10−7 M), TRPV3 (ruthenium red, IC50 2.5 × 10−7 M), TRPA1 (ruthenium red, 10 µM), TRPM3 (isosakuranetin, 10 µM; IC50 50 nM), ASIC3 (amiloride, 1 mM). ª The observed antagonism could be due, at least in part, to desensitization, since the compound is able to activate the receptor > 20%
CME and TV: Investigation, Formal analysis, Writing—review & editing. MAB and AMP: Investigation, Writing—review & editing. AFM: Supervision, Funding acquisition, Writing—review & editing. AFC: Supervision, Funding acquisition, Writing—original draft, Writing—review & editing. RGM: Conceptualization, Supervision, Funding acquisition, Writing—original draft, Writing—review & editing. All authors read and approved the submitted version.
Conflicts of interest
Rosario González-Muñiz, the Editorial Board Member of Exploration of Drug Science and Guest Editor of the special issue—Mimicking Nature: Biomimetics as Tools for Diagnosis and Therapeutics, had no involvement in the journal review process of this manuscript. The other authors declare that they have no conflicts of interest.
Ethical approval
Animal experimentation procedures were conducted under the approval of the Institutional Animal and Ethical Committee at UMH (UMH.IDI.AFM.06.20), and approved by the Generalitat Valenciana (2021/VSC/PEA/0089).
Consent to participate
Not applicable.
Consent to publication
Not applicable.
Availability of data and materials
Most data from this paper are included in this manuscript and the supplementary materials. Additional data could be obtained from the authors upon request.
Funding
This research was funded by FEDER [MCIN/AEI/10.13039/501100011033]; Una manera de hacer Europa [PID2021-126423OB-C21, to AFM and AFC], [PID2021-126423OB-C22, to RGM]; Generalitat Valenciana [PROMETEO/2021/031, to AFM]; CSIC [202180E073, to RGM]; and Comunidad de Madrid [IND2017/BMD7673, to RGM]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.
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