Inflammatory acidic pH enhances hydrogen sulfide-induced transient receptor potential ankyrin 1 activation in RIN-14B...

Hydrogen sulfide (H2 S), a toxic volcanic gas, functions as a gaseous physiological and pathophysiological molecule. Recently we have shown that H2 S elicits acute pain through the activation of transient receptor potential ankyrin 1 (TRPA1), which is expressed mainly in primary nociceptive neurons. We also demonstrated enhancement of H2 S-induced TRPA1 activation and pain under inflammatory acidic conditions, but the underlying mechanism has not been elucidated. Here, we attempted to clarify this mechanism by using endogenously TRPA1-expressing RIN-14B, a rat pancreatic islet cell line. For this purpose, the intracellular Ca(2+) concentration ([Ca(2+) ]i )], reactive oxygen species (ROS), and intracellular pH (pHi ) were measured with fluorescent imaging techniques. The intracellular H2 S concentration was assayed by the methylene blue method. To clarify the cellular function of H2 S, 5-hydroxytryptamine (5-HT) secretion was analyzed. In RIN-14B, the increase of [Ca(2+) ]i and the release of 5-HT induced by NaHS, an H2 S donor, were enhanced under inflammatory acidic conditions. Transition of H2 S into cells was enhanced at pH 6.8. H2 S failed to increase the intracellular ROS level and only slightly decreased pHi . These results suggest that H2 S directly activates TRPA1 and that its increment of diffusion into cells may be involved in the potentiation of TRPA1 activation under external acidic conditions. Thus, our study supports the pathophysiological functions of H2 S in inflammatory pain.