Background: Chloroquine (CQ) evokes the sensation of itch by exciting peripheral sensory neurons. Results: CQ not only directly excites a diverse population of sensory neurons but also strongly modulates ion channels involved in pain and itch transduction. Conclusion: CQ exerts widespread actions on peripheral sensory neurons. Significance: Our results increase our understanding of the action of CQ on sensory neurons.

TRPA1 is a Ca2+-permeable ion channel involved in many sensory disorders such as pain, itch and neuropathy. Notably, the function of TRPA1 depends on Ca2+, with low Ca2+ potentiating and high Ca2+ inactivating TRPA1. However, it remains unknown how Ca2+ exerts such contrasting effects. Here, we show that Ca2+ regulates TRPA1 through calmodulin, which binds to TRPA1 in a Ca2+-dependent manner. Calmodulin binding enhanced TRPA1 sensitivity and Ca2+-evoked potentiation of TRPA1 at low Ca2+, but inhibited TRPA1 sensitivity and promoted TRPA1 desensitization at high Ca2+. Ca2+-dependent potentiation and inactivation of TRPA1 were selectively prevented by disrupting the interaction of the carboxy-lobe of calmodulin with a calmodulin-binding domain in the C-terminus of TRPA1. Calmodulin is thus a critical Ca2+ sensor enabling TRPA1 to respond to diverse Ca2+ signals distinctly.

In the present study, antioxidant potential of the methanol extract of the leaves of Mimusops elengi Linn. was evaluated by using 1, 1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay, reducing power and total antioxidant capacity. The extract showed significant activities in all antioxidant assays compared to the reference antioxidant ascorbic acid in a dose dependent manner. In DPPH scavenging assay the IC50 value of the extract was found to be 43.26µg/ml while the IC50 value of the reference standard ascorbic acid was 58.92 µg/ml. Total antioxidant activity was also found to increase in a dose dependent manner. Moreover, M. elengi extract showed strong reducing power. These results suggest that Mimusops elengi may act as a chemopreventative agent, providing antioxidant properties and offering effective protection from free radicals.