Capsaicin-Sensitive Sensory Nerves Mediate the Cellular and Microvascular Effects of H sub(2)S via TRPA1 Receptor Activation and Neuropeptide Release

It is supposed that TRPA1 receptor can be activated by hydrogen sulphide (H sub(2)S). Here, we have investigated the role of TRPA1 receptor in H sub(2)S-induced [Ca super(2+)] sub(i) increase in trigeminal ganglia (TRG) neurons, and the involvement of capsaicin-sensitive sensory nerves in H sub(2)S-evoked cutaneous vasodilatation. [Ca super(2+)] sub(i) was measured with ratiometric technique on TRG neurons of TRPA1 super(+/+) and TRPA1 super(-/-) mice after NaHS, Na sub(2)S, allylisothiocyanate (AITC) or KCl treatment. Microcirculatory changes in the ear were detected by laser Doppler imaging in response to topical NaHS, AITC, NaOH, NaSO sub(3) or NaCl. Mice were either treated with resiniferatoxin (RTX), or CGRP antagonist BIBN4096, or NK sub(1) receptor antagonist CP99994, or K super(+) sub(ATP) channel blocker glibenclamide. Alpha-CGRP super(-/-) and NK sub(1) super(-/-) mice were also investigated. NaHS and Na sub(2)S increased [Ca super(2+)] sub(i) in TRG neurons derived from TRPA super(+/+) but not from TRPA1 super(-/-) mice. NaHS increased cutaneous blood flow, while NaOH, NaSO sub(3) 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 super(-/-) or NK sub(1) super(-/-) mice compared to wild-types. H sub(2)S 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.