Payrits, Maja and Horváth, Ádám and Biró-Sütő, Tünde and Erostyák, János and Makkai, Géza and Sághy, Éva and Pohóczky, Krisztina and Kecskés, Angéla and Kecskés, Miklós and Szolcsányi, János and Helyes, Zsuzsanna and Szőke, Éva (2020) Resolvin D1 and D2 inhibit transient receptor potential vanilloid 1 and ankyrin 1 ion channel activation on sensory neurons via lipid raft modification. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21 (14). ISSN 1661-6596
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Abstract
Transient Receptor Potential Vanilloid 1 and Ankyrin 1 (TRPV1, TRPA1) cation channels are expressed in nociceptive primary sensory neurons and regulate nociceptor and inflammatory functions. Resolvins are endogenous lipid mediators. Resolvin D1 (RvD1) is described as a selective inhibitor of TRPA1-related postoperative and inflammatory pain in mice acting on the G protein-coupled receptor DRV1/GPR32. Resolvin D2 (RvD2) is a very potent TRPV1 and TRPA1 inhibitor in DRG neurons, and decreases inflammatory pain in mice acting on the GPR18 receptor, via TRPV1/TRPA1-independent mechanisms. We provided evidence that resolvins inhibited neuropeptide release from the stimulated sensory nerve terminals by TRPV1 and TRPA1 activators capsaicin (CAPS) and allyl-isothiocyanate (AITC), respectively. We showed that RvD1 and RvD2 in nanomolar concentrations significantly decreased TRPV1 and TRPA1 activation on sensory neurons by fluorescent calcium imaging and inhibited the CAPS-and AITC-evoked45Ca-uptake on TRPV1-and TRPA1-expressing CHO cells. Since CHO cells are unlikely to express resolvin receptors, resolvins are suggested to inhibit channel opening through surrounding lipid raft disruption. Here, we proved the ability of resolvins to alter the membrane polarity related to cholesterol composition by fluorescence spectroscopy. It is concluded that targeting lipid raft integrity can open novel peripheral analgesic opportunities by decreasing the activation of nociceptors. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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| Additional Information: | Funding Agency and Grant Number: National Brain Research Program [2017-1.2.1-NKP-2017-00002]; Hungarian Government [GINOP-2.3.2-15-2016-00050, EFOP-3.6.2-16-2017-00006, EFOP-3.6.2-16-2017-00008]; Janos Bolyai Research Scholarship of the Hungarian Academy of SciencesHungarian Academy of Sciences; University of Pecs [17886-4/23018/FEKUTSTRAT]; New National Excellence Program of the ministry of Human Capacities [UNKP-18-4]; New National Excellence Program of the ministry for Innovation and Technology [UNKP-19-4] Funding text: This work was supported by the National Brain Research Program 2017-1.2.1-NKP-2017-00002 (NAP-2; Chronic Pain Research Group). We acknowledge the grant of the Hungarian Government (GINOP-2.3.2-15-2016-00050, EFOP-3.6.2-16-2017-00006 and EFOP-3.6.2-16-2017-00008). E. Szoke A. Kecskes and E. Saghy were supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences. The University of Pecs is acknowledged for a support by the 17886-4/23018/FEKUTSTRAT excellence grant. M. Payrits was supported by the New National Excellence Program of the ministry of Human Capacities UNKP-18-4. E. Szoke and E. Saghy were supported by the New National Excellence Program of the ministry of Human Capacities UNKP-18-4 and New National Excellence Program of the ministry for Innovation and Technology UNKP-19-4 grant. Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti str. 12, Pécs, H-7624, Hungary János Szentágothai Research Centre and Centre for Neuroscience, University of Pécs, Ifjúság str. 20, Pécs, H-7624, Hungary Department of Experimental Physics, Faculty of Sciences, University of Pécs, Ifjúság str. 6, Pécs, H-7624, Hungary Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad sq. 4, Budapest, H-1089, Hungary Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Szigeti str. 12, Pécs, H-7624, Hungary Institute of Physiology, Medical School, University of Pécs, Szigeti str. 12, Pécs, H-7624, Hungary Export Date: 22 September 2020 Correspondence Address: Horváth, Á.; Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, János Szentágothai Research Centre and Centre for Neuroscience, University of Pécs, Szigeti str. 12, Hungary; email: horvatadam7@gmail.com |
| Uncontrolled Keywords: | LIPID RAFTS; transient receptor potential channel; sensory neuron; resolvin D1; nerve terminal; Resolvin D2; |
| Subjects: | Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3015 Molecular biology / molekuláris biológia R Medicine / orvostudomány > RC Internal medicine / belgyógyászat > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry / idegkórtan, neurológia, pszichiátria R Medicine / orvostudomány > RS Pharmacy and materia medica / gyógyszerészet, gyógyászati eszközök |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 28 Sep 2020 06:46 |
| Last Modified: | 28 Sep 2020 06:46 |
| URI: | http://real.mtak.hu/id/eprint/114946 |
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