New Insights on Formyl Peptide Receptor Type 2 Involvement in Nociceptive Processes in the Spinal Cord
Formyl peptide receptor type 2 (FPR2/ALX) belongs to the formyl peptide receptors (FPRs) family clustered on chromosome 19 and encodes a family of three Class A of G protein-coupled receptors (GPCRs). A short N-terminal region, an NPXXY motif in transmembrane (TM) region 7 and an E/DRY motif that br...
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MDPI AG
2022-03-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/12/4/500 |
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| author | Mariantonella Colucci Azzurra Stefanucci Adriano Mollica Anna Maria Aloisi Francesco Maione Stefano Pieretti |
| author_facet | Mariantonella Colucci Azzurra Stefanucci Adriano Mollica Anna Maria Aloisi Francesco Maione Stefano Pieretti |
| author_sort | Mariantonella Colucci |
| collection | DOAJ |
| description | Formyl peptide receptor type 2 (FPR2/ALX) belongs to the formyl peptide receptors (FPRs) family clustered on chromosome 19 and encodes a family of three Class A of G protein-coupled receptors (GPCRs). A short N-terminal region, an NPXXY motif in transmembrane (TM) region 7 and an E/DRY motif that bridges TM3 and TM6 stabilizing inactive receptor conformations characterize this class of receptors. In recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), FPRs play a crucial role in innate immune responses. FPR2/ALX is highly expressed in myeloid cells, as well as in chondrocytes, fibroblasts, endothelial, epithelial and smooth muscle cells. FPR2/ALX mRNA expression was recently reported in the rat brainstem, spinal cord, thalamus/hypothalamus, cerebral neocortex, hippocampus, cerebellum and striatum. The central nervous system (CNS) distribution of FPR2/ALX suggests important functions in nociception. Thus, the present study was carried out to investigate the possible role of FPR2/ALX in nociception in mice. Intrathecal administration of the formyl peptide receptor type 1 (FPR1) agonist fMLF and the FPR2/ALX agonist BML-111 relieved nociception and these effects were reduced by contemporary administration of the FPR2/ALX antagonist WRW<sup>4</sup>. Furthermore, measurement of cytokines and brain-derived neurotrophic factor (BDNF) in the spinal cord of neuropathic mice demonstrated that the antinociceptive effects of BML-111 might depend on the reduction in cytokine release and BDNF in the spinal cord. These results suggest a possible role of FPR2/ALX for pain control in the spinal cord. |
| first_indexed | 2024-03-09T10:32:57Z |
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| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T10:32:57Z |
| publishDate | 2022-03-01 |
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| record_format | Article |
| series | Life |
| spelling | doaj.art-53ebae628e0b4ff98a0fb640d60103fb2023-12-01T21:09:54ZengMDPI AGLife2075-17292022-03-0112450010.3390/life12040500New Insights on Formyl Peptide Receptor Type 2 Involvement in Nociceptive Processes in the Spinal CordMariantonella Colucci0Azzurra Stefanucci1Adriano Mollica2Anna Maria Aloisi3Francesco Maione4Stefano Pieretti5National Centre for Drug Research and Evaluation, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, ItalyDepartment of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, ItalyDepartment of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, ItalyImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80138 Naples, ItalyNational Centre for Drug Research and Evaluation, Istituto Superiore di Sanità, 00161 Rome, ItalyFormyl peptide receptor type 2 (FPR2/ALX) belongs to the formyl peptide receptors (FPRs) family clustered on chromosome 19 and encodes a family of three Class A of G protein-coupled receptors (GPCRs). A short N-terminal region, an NPXXY motif in transmembrane (TM) region 7 and an E/DRY motif that bridges TM3 and TM6 stabilizing inactive receptor conformations characterize this class of receptors. In recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), FPRs play a crucial role in innate immune responses. FPR2/ALX is highly expressed in myeloid cells, as well as in chondrocytes, fibroblasts, endothelial, epithelial and smooth muscle cells. FPR2/ALX mRNA expression was recently reported in the rat brainstem, spinal cord, thalamus/hypothalamus, cerebral neocortex, hippocampus, cerebellum and striatum. The central nervous system (CNS) distribution of FPR2/ALX suggests important functions in nociception. Thus, the present study was carried out to investigate the possible role of FPR2/ALX in nociception in mice. Intrathecal administration of the formyl peptide receptor type 1 (FPR1) agonist fMLF and the FPR2/ALX agonist BML-111 relieved nociception and these effects were reduced by contemporary administration of the FPR2/ALX antagonist WRW<sup>4</sup>. Furthermore, measurement of cytokines and brain-derived neurotrophic factor (BDNF) in the spinal cord of neuropathic mice demonstrated that the antinociceptive effects of BML-111 might depend on the reduction in cytokine release and BDNF in the spinal cord. These results suggest a possible role of FPR2/ALX for pain control in the spinal cord.https://www.mdpi.com/2075-1729/12/4/500annexinformyl peptide receptorsnociceptionpainspinal cord |
| spellingShingle | Mariantonella Colucci Azzurra Stefanucci Adriano Mollica Anna Maria Aloisi Francesco Maione Stefano Pieretti New Insights on Formyl Peptide Receptor Type 2 Involvement in Nociceptive Processes in the Spinal Cord Life annexin formyl peptide receptors nociception pain spinal cord |
| title | New Insights on Formyl Peptide Receptor Type 2 Involvement in Nociceptive Processes in the Spinal Cord |
| title_full | New Insights on Formyl Peptide Receptor Type 2 Involvement in Nociceptive Processes in the Spinal Cord |
| title_fullStr | New Insights on Formyl Peptide Receptor Type 2 Involvement in Nociceptive Processes in the Spinal Cord |
| title_full_unstemmed | New Insights on Formyl Peptide Receptor Type 2 Involvement in Nociceptive Processes in the Spinal Cord |
| title_short | New Insights on Formyl Peptide Receptor Type 2 Involvement in Nociceptive Processes in the Spinal Cord |
| title_sort | new insights on formyl peptide receptor type 2 involvement in nociceptive processes in the spinal cord |
| topic | annexin formyl peptide receptors nociception pain spinal cord |
| url | https://www.mdpi.com/2075-1729/12/4/500 |
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