ABSTRACT TRPA1 receptors sense chemical irritants, but they do not normally respond to light. Previous studies have identified compounds that confer photosensitivity onto vertebrate TRPA1. However, the pharmacology of TRPA1-mediated non-visual photosensation remains poorly understood. To identify novel compounds that affect this process, we screened a large chemical library for compounds that increased light-elicited motor activity in larval zebrafish. We found structurally diverse hit compounds that were photoreactive and produced specific behavioral phenotypes. A subset of these compounds required functional TRPA1 to produce behavioral phenotypes in vivo. These findings provide novel prototype compounds for controlling TRPA1 with light and improve our understanding of non-visual TRPA1-mediated photosensation.
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