The role of transient receptor potential ankyrin 1 (TRPA1) receptor activation in hydrogen-sulphide-induced CGRP-release and vasodilation.
Activation of transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) channels on capsaicin-sensitive sensory neurons causes release of inflammatory neuropeptides, including calcitonin gene-related peptide (CGRP). We investigated whether the hydrogen sulphide (H(2)S)-evoked CGRP release from sensory neurons of isolated rat tracheae and H(2)S-induced increases in the microcirculation of the mouse ear were mediated by TRPA1 receptor activation. Allylisothiocyanate (AITC) or the H(2)S donor sodium hydrogen sulphide (NaHS) were used as stimuli and CGRP release of the rat tracheae was measured by radioimmunoassay. AITC or NaHS were applied to the ears of Balb/c, C57BL/6, TRPA1 and TRPV1 receptor gene knockout mice and blood flow was detected by laser Doppler imaging. Both AITC and NaHS increased CGRP release from isolated rat tracheae, and both responses were inhibited by the TRPA1 antagonist, HC-030031, but was not affected by the TRPV1 receptor blocker, BCTC. Application of AITC or NaHS increased the cutaneous blood flow in the mouse ears. Similarly to the effect of AITC, the vasodilatory response to NaHS was reduced by HC-030031 or in TRPA1 deleted mice. In contrast, genetic deletion of TRPV1 did not affect the increase in the ear blood flow evoked by AITC or NaHS. We conclude that H(2)S activates TRPA1 receptors causing CGRP release from sensory nerves of rat tracheae, as well as inducing cutaneous vasodilatation in the mouse ear. TRPV1 receptors were not involved in these processes. Our results highlight that TRPA1 receptor activation should be considered as a potential mechanism of vasoactive effects of H(2)S.
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, H-7624, Pécs, Szigeti u. 12., Hungary.
Gábor
G
Pozsgai
Zsófia
Z
Hajna
Teréz
T
Bagoly
Melinda
M
Boros
Ágnes
Á
Kemény
Serena
S
Materazzi
Romina
R
Nassini
Zsuzsanna
Z
Helyes
János
J
Szolcsányi
Erika
E
Pintér
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D005260:Female; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D017208:Rats, Wistar; D000074025:TRPA1 Cation Channel; D014132:Trachea / Q000294:innervation / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000378:metabolism / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*
D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D015740:Calcitonin Gene-Related Peptide; D006862:Hydrogen Sulfide