Bioinformatic and behavioral analysis of Pannexin 1 involvement in cutaneous perception in mice

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

To reveal new functions of pannexin 1 in the mouse nervous system, cell types with the most pronounced expression of the gene encoding this protein were identified by bioinformatic analysis. It turned out that sensory neurons PSNP3 and PSNP6 of the dorsal root ganglia have the highest expression levels of Panx1, as well as high expression of purinoreceptor p2rx3, and other genes associated with the perception of pain and skin itch. The scratch reflex induced by compound 48/80 was suppressed in Panx1 knockout mice compared to wild-type mice, confirming the involvement of Panx1 in the purinergic regulation of sensory nerve fibers responsible for itch perception.

Full Text

Restricted Access

About the authors

O. O. Kiryukhina

A.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences

Author for correspondence.
Email: kcyu@yandex.ru
Russian Federation, Bolshoy Karetny pereulok, 19, building 1, Moscow, 127051 Russia

O. S. Tarasova

Institute of Biomedical Problems, Russian Academy of Sciences; Moscow State University named after M.V. Lomonosov

Email: kcyu@yandex.ru
Russian Federation, Khoroshevskoe shosse, 76A, Moscow, 123007; Lomonosovsky Prospekt, 27, Bldg. 1, Moscow, 119991

Yu. V. Panchin

A.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences; Research Institute of Physical Chemistry and Biology named after A.N. Belozersky

Email: kcyu@yandex.ru
Russian Federation, Bolshoy Karetny pereulok, 19, building 1, Moscow, 127051; Leninskie Gory, 1, Bldg. 40, Moscow, 119234 Russia

References

  1. Battulin N., Kovalzon V. M., Korablev A., Serova I., Kiryukhina O. O., Pechkova M. G., Bogotskoy K. A., Tarasova O. S., Panchin Y. Pannexin 1 transgenic mice: human diseases and sleep-wake function revision // Int. J. Mol. Sci. 2021. V. 22. № 10. P. 5269. https://doi.org/10.3390/ijms22105269
  2. Broccardo M., Erspamer V., Falconieri Erspamer G., Improta G., Linari G., Melchiorri P., Montecucchi P. C. Pharmacological data on dermorphins, a new class of potent opioid peptides from amphibian skin // Br. J. Pharmacol. 1981. V. 73. № 3. P. 625–31. https://doi.org/10.1111/j.1476-5381.1981.tb16797.x
  3. Burnstock G. Discovery of purinergic signalling, the initial resistance and current explosion of interest // Br. J. Pharmacol. 2012. V. 167. № 2. P. 238–255. https://doi.org/10.1111/j.1476-5381.2012.02008.x
  4. Chen C. C., Akopian A. N., Sivilotti L., Colquhoun D., Burnstock G., Wood J. N. A P2X purinoceptor expressed by a subset of sensory neurons // Nature. 1995. V. 377. № 6548. P. 428–31. https://doi.org/10.1038/377428a0
  5. Chiu Y. H., Schappe M. S., Desai B. N., Bayliss D. A. Revisiting multimodal activation and channel properties of Pannexin 1 // Journal of General Physiology. 2018. V. 150. № 1. P. 19–39. https://doi.org/10.1085/jgp.201711888
  6. Cranfill S. L., Luo W. The development of somatosensory neurons: Insights into pain and itch // Curr Top Dev Biol. 2021. V. 142 P. 443-475. https://doi.org/10.1016/bs.ctdb.2020.10.005
  7. Dahl G. ATP release through pannexon channels // Philosophical Transactions of the Royal Society B Biological Sciences. 2015. V. 370. № 1672. P. 20140191. https://doi.org/10.1098/rstb.2014.0191
  8. Guo C., Jiang H., Huang C. C., Li F., Olson W., Yang W., Fleming M., Yu G., Hoekel G., Luo W., Liu Q. Pain and itch coding mechanisms of polymodal sensory neurons // Cell Rep. 2023. V. 42. № 11. P. 113316. https://doi.org/10.1016/j.celrep.2023.113316
  9. Hung S. C., Choi C. H., Said-Sadier N., Johnson L., Atanasova K. R., Sellami H., Yilmaz Ö., Ojcius D. M. P2X4 assembles with P2X7 and pannexin-1 in gingival epithelial cells and modulates ATP-induced reactive oxygen species production and inflammasome activation // PLoS One. 2013. V. 8. № 7. P. e70210. https://doi.org/10.1371/journal.pone.0070210
  10. Iglesias R., Locovei S., Roque A., Alberto A. P., Dahl G., Spray D. C., Scemes E. P2X7 receptor-Pannexin1 complex: pharmacology and signaling // Am J Physiol Cell Physiol. 2008. V. 295. № 3. P. C752–60. https://doi.org/10.1152/ajpcell.00228.2008
  11. Inoue K. The Role of ATP Receptors in Pain Signaling // Neurochem Res. 2022. V. 47. № 9. P. 2454–2468. https://doi.org/10.1007/s11064-021-03516-6
  12. Kittaka H., Tominaga M. The molecular and cellular mechanisms of itch and the involvement of TRP channels in the peripheral sensory nervous system and skin // Allergol Int. 2017. V. 66. № 1. P. 22–30. https://doi.org/10.1016/j.alit.2016.10.003
  13. Liu Q., Sikand P., Ma C., Tang Z., Han L., Li Z., Sun S., LaMotte R.H., Dong X. Mechanisms of itch evoked by β-alanine // J Neurosci. 2012. V. 32, № 42. P. 14532-7. doi: 10.1523/JNEUROSCI.3509-12.2012
  14. McAllister B.B., Stokes-Heck S., Harding E. K., van den Hoogen N. J., Trang T. Targeting Pannexin-1 Channels: Addressing the ‘Gap’ in Chronic Pain // CNS Drugs. 2024. V. 38. № 2. P. 77–91. https://doi.org/10.1007/s40263-024-01061-8
  15. Mishra S. K., Hoon M. A. The cells and circuitry for itch responses in mice // Science. 2013. V. 340. № 6135. P. 968–71. https://doi.org/10.1126/science.1233765
  16. Nocchi L., Roy N., D’Attilia M., Dhandapani R., Maffei M., Traista A., Castaldi L., Perlas E., Chadick C. H., Heppenstall P. A. Interleukin-31-mediated photoablation of pruritogenic epidermal neurons reduces itch-associated behaviours in mice // Nat Biomed Eng. 2019. V. 3. № 2. P. 114–125. https://doi.org/10.1038/s41551-018-0328-5
  17. Panchin Y., Kelmanson I., Matz M., Lukyanov K., Usman N., Lukyanov S. A. Ubiquitous family of putative gap junction molecules // Current Biology. 2000. V. 10. № 12. P. R473–474. https://doi.org/10.1016/s0960-9822(00)00576-5
  18. Pelegrin P., Surprenant A. Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor // MBO J. 2006. V. 25. № 21. P. 5071–82. https://doi.org/10.1038/sj.emboj.7601378
  19. Ralevic V., Burnstock G. Receptors for purines and pyrimidines // Pharmacological Reviews. 1998. V. 50. № 3. P. 413–492.
  20. Schemann M., Kugler E. M., Buhner S., Eastwood C., Donovan J., Jiang W., Grundy D. The mast cell degranulator compound 48/80 directly activates neurons // PLoS One. 2012. V. 7. № 12. P. e52104. https://doi.org/10.1371/journal.pone.0052104
  21. Shao Q., Lindstrom K., Shi R., Kelly J., Schroeder A., Juusola J., Levine K. L., Esseltine J. L., Penuela S., Jackson M. F., Laird D. W. A germline variant in the PANX1 gene has reduced channel function and is associated with multisystem dysfunction // Journal of Biological Chemistry. 2016. V. 291. № 24. P. 12432–12443. https://doi.org/10.1074/jbc.M116.717934
  22. Shiratori-Hayashi M., Hasegawa A., Toyonaga H., Andoh T., Nakahara T., Kido-Nakahara M., Furue M., Kuraishi Y., Inoue K., Dong X., Tsuda M. Role of P2X3 receptors in scratching behavior in mouse models // J Allergy Clin Immunol. 2019. V. 143. № 3. P. 1252–1254. https://doi.org/10.1016/j.jaci.2018.10.053
  23. Sun Y. G., Zhao Z. Q., Meng X. L., Yin J., Liu X. Y., Chen Z. F. Cellular basis of itch sensation // Science. 2009. V. 325. № 5947 P. 1531–4. https://doi.org/10.1126/science.1174868
  24. Tansey E. A., Johnson C. D. Recent advances in thermoregulation // Adv Physiol Educ. 2015. V. 39, № 3. P. 139–48. https://doi.org/10.1152/advan.00126.2014
  25. Uchida H., Nagai J., Ueda H. Lysophosphatidic acid and its receptors LPA1 and LPA3 mediate paclitaxel-induced neuropathic pain in mice // Mol Pain. 2014. 10:71. https://doi.org/10.1186/1744-8069-10-71
  26. Wang W., Qu R., Dou Q., Wu F., Wang W., Chen B., Mu J., Zhang Z., Zhao L., Zhou Z., Dong J., Zeng Y., Liu R., Du J., Zhu S., Li Q., He L., Jin L., Wang L., Sang Q. Homozygous variants in PANX1 cause human oocyte death and female infertility // Eur J Hum Genet. 2021. V. 29. № 9. P. 1396–1404. https://doi.org/10.1038/s41431-020-00807-4
  27. Zeisel A., Hochgerner H., Lönnerberg P., Johnsson A., Memic F., van der Zwan J., Häring M., Braun E., Borm L. E., La Manno G., Codeluppi S., Furlan A., Lee K., Skene N., Harris K. D., Hjerling-Leffler J., Arenas E., Ernfors P., Marklund U., Linnarsson S. Molecular Architecture of the Mouse Nervous System // Cell. 2018. V. 174. № 4. P. 999–1014. https://doi.org/10.1016/j.cell.2018.06.021
  28. Zhang Y., Laumet G., Chen S. R., Hittelman W. N., Pan H. L. Pannexin-1 Up-regulation in the Dorsal Root Ganglion Contributes to Neuropathic Pain Development // J Biol Chem. 2015. V. 290. № 23. P. 14647–55. https://doi.org/10.1074/jbc.M115.650218

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Effect of injection of physiological saline (f/r) and substance 48/80 (48/80) on the scratching reflex in C57Bl/6J mice (WT) (a, b) and Panx1 knockout (KO) (c, d). Number of scratching acts summed up for 30 min before and after injection of substances (a, c); total scratching time for 30 min before and after injection of substances (b, d). Data are presented as median and interquartile range. # – p<0.05 – comparison of scratching parameters before and after injection of substance (Wilcoxon test with Bonferroni correction). * – p<0.05 – comparison of scratching parameters after administration of physiological saline and substance 48/80 (Mann-Whitney test with Bonferroni correction).

Download (1MB)
Indexing metadata
3. Fig. 2. Dynamics of scratching reflex activation in C57Bl/6J (WT) and Panx1 knockout (KO) mice after injection of 48/80. The number of scratching acts summed up over 10-min time intervals (a); total scratching time over 10 min (b). Data are presented as median and interquartile range. * – p<0.05 – comparison of WT and KO groups at three time points after administration of 48/80 (according to the Mann–Whitney test with Bonferroni correction).

Download (704KB)
Indexing metadata
4. Fig. 3. Thermosensitivity indices (time to paw licking) in C57Bl/6J (WT) and Panx1 knockout (KO) mice in the hot plate test. Data are presented as median and interquartile range. No statistically significant differences were found between the groups (according to the Mann–Whitney test with Bonferroni correction).

Download (319KB)
Indexing metadata

Copyright (c) 2025 Russian Academy of Sciences