Capsaicin-Sensitive Sensory Nerves Mediate the Cellular and Microvascular Effects of H2S via TRPA1 Receptor Activation and Neuropeptide Release
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It is supposed that TRPA1 receptor can be activated by hydrogen sulphide (H2S). Here, we have investigated the role of TRPA1 receptor in H2S-induced [Ca2+]i increase in trigeminal ganglia (TRG) neurons, and the involvement of capsaicin-sensitive sensory nerves in H2S-evoked cutaneous vasodilatation. [Ca2+]i was measured with ratiometric technique on TRG neurons of TRPA1+/+ and TRPA1−/− mice after NaHS, Na2S, allylisothiocyanate (AITC) or KCl treatment. Microcirculatory changes in the ear were detected by laser Doppler imaging in response to topical NaHS, AITC, NaOH, NaSO3 or NaCl. Mice were either treated with resiniferatoxin (RTX), or CGRP antagonist BIBN4096, or NK1 receptor antagonist CP99994, or K+ ATP channel blocker glibenclamide. Alpha-CGRP−/− and NK1 −/− mice were also investigated. NaHS and Na2S increased [Ca2+]i in TRG neurons derived from TRPA+/+ but not from TRPA1−/− mice. NaHS increased cutaneous blood flow, while NaOH, NaSO3 and NaCl did not cause significant changes. NaHS-induced vasodilatation was reduced in RTX-treated animals, as well as by pre-treatment with BIBN4096 or CP99994 alone or in combination. NaHS-induced vasodilatation was significantly smaller in alpha-CGRP−/− or NK1 −/− mice compared to wild-types. H2S activates capsaicin-sensitive sensory nerves through TRPA1 receptors and the resultant vasodilatation is mediated by the release of vasoactive sensory neuropeptides CGRP and substance P.
KeywordsCapsaicin-sensitive sensory neuron CGRP Hydrogen sulphide Substance P TRPA1 receptor
calcitonin gene-related peptide
Chinese hamster ovary
counts per minute
dorsal root ganglion
Transient Receptor Potential Ankyrin 1
Transient Receptor Potential Vanilloid 1
The present scientific work is dedicated to the 650th anniversary of the foundation of the University of Pécs, Hungary.
This study was supported by Hungarian Research Grant “OTKA NN-114458”, by the Hungarian Brain Research Program and National Development Agency KTIA_NAP_13-1-2013-0001, and MTA-PTE NAP B Chronic Pain Research Group, 888819. E. Pintér was supported by János Szentágothai Scholarship (A2-SZJÖ-TOK-13-0149) of the Hungarian National Excellence Program TÁMOP-4.2.4. A/2-11-1-2012-0001. A. A. Aubdool is supported by the British Heart Foundation PG/12/34/29557. É. Sághy and M. Payrits were supported by Gedeon Richter's Talentum Foundation.
Z. Hajna, É. Szőke, G. Pozsgai, L. Nagy, Z. Helyes, S.D. Brain and E. Pintér contributed to the conception and design of research; Z. Hajna, É. Sághy, M. Payrits, A.A. Aubdool, G. Pozsgai, I.Z. Bátai, L. Nagy and D. Filotás performed the experiments and analysed the data; Z. Hajna, A.A. Aubdool, É. Szőke, G. Pozsgai, L. Nagy, Z. Helyes, S.D. Brain and E. Pintér interpreted the results of experiments; Z. Hajna, É. Sághy, M. Payrits, A.A. Aubdool prepared the figures; Z. Hajna, É. Sághy, M. Payrits and E. Pintér drafted the manuscript; Z. Hajna, A.A. Aubdool, É. Szőke, G. Pozsgai, Z. Helyes, S.D. Brain and E. Pintér edited and revised the manuscript; E. Pintér approved the final version of the manuscript.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
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