title: Capsaicin-Sensitive Sensory Nerves Mediate the Cellular and Microvascular Effects of H2S via TRPA1 Receptor Activation and Neuropeptide Release.
abstract: 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 [Ca(2+)]i increase in trigeminal ganglia (TRG) neurons, and the involvement of capsaicin-sensitive sensory nerves in H2S-evoked cutaneous vasodilatation. [Ca(2+)]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 [Ca(2+)]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.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti út 12, Pécs, H-7624, Hungary.|János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs, H-7624, Hungary.
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Hajna
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti út 12, Pécs, H-7624, Hungary.|János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs, H-7624, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Sághy
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti út 12, Pécs, H-7624, Hungary.|János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs, H-7624, Hungary.
authors.forename: Maja
authors.initials: M
authors.lastname: Payrits
authors.affiliation: BHF Cardiovascular Centre of Excellence and Centre of Integrative Biomedicine, King's College London, London, SE1 9NH, UK.
authors.forename: Aisah A
authors.initials: AA
authors.lastname: Aubdool
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti út 12, Pécs, H-7624, Hungary.|János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs, H-7624, Hungary.|MTA-PTE NAP B Chronic Pain Research Group, Pécs, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Szőke
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti út 12, Pécs, H-7624, Hungary.|János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs, H-7624, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Pozsgai
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti út 12, Pécs, H-7624, Hungary.|János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs, H-7624, Hungary.
authors.forename: István Z
authors.initials: IZ
authors.lastname: Bátai
authors.affiliation: János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs, H-7624, Hungary.
authors.forename: Lívia
authors.initials: L
authors.lastname: Nagy
authors.affiliation: Department of General and Physical Chemistry, Faculty of Sciences, University of Pécs, Ifjúság útja 6, Pécs, H-7624, Hungary.
authors.forename: Dániel
authors.initials: D
authors.lastname: Filotás
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti út 12, Pécs, H-7624, Hungary.|János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs, H-7624, Hungary.|MTA-PTE NAP B Chronic Pain Research Group, Pécs, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Helyes
authors.affiliation: BHF Cardiovascular Centre of Excellence and Centre of Integrative Biomedicine, King's College London, London, SE1 9NH, UK.
authors.forename: Susan D
authors.initials: SD
authors.lastname: Brain
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti út 12, Pécs, H-7624, Hungary. erika.pinter@aok.pte.hu.|János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs, H-7624, Hungary. erika.pinter@aok.pte.hu.
authors.forename: Erika
authors.initials: E
authors.lastname: Pintér
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D004151:Dipeptides / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014664:Vasodilation
chemical_list: C505165:1-(N(2)-(3,4-dibromo-N-((4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl)carbonyl)tyrosyl)lysyl)-4-(4-pyridinyl)piperazine; D004151:Dipeptides; D004224:Diterpenes; D064729:Neurokinin-1 Receptor Antagonists; D011799:Quinazolines; D018040:Receptors, Neurokinin-1; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D013373:Substance P; D011189:Potassium Chloride; C024353:resiniferatoxin; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D005905:Glyburide; D006862:Hydrogen Sulfide
keywords: CGRP; Capsaicin-sensitive sensory neuron; Hydrogen sulphide; Substance P; TRPA1 receptor