Diethylcarbamazine elicits calcium signals by activation of Brugia malayi TRP-2b channels heterologously expressed in HEK293 cells

Diethylcarbamazine is a classic anthelmintic that is used for the prevention and treatment of lymphatic filariasis. The mode of action of diethylcarbamazine is still not well understood with the consensus that it acts on the host immune system, rather than directly acting on the adult parasite. Recent studies, have found that diethylcarbamazine acts on the muscle of adult female Brugia malayi , generating temporary spastic paralysis mainly through the Transient Potential Receptor C (TRPC) orthologue TRP-2. Activation of TRP-2 leads to inward currents on the muscle, an increase in intracellular calcium and subsequent muscle contraction. These studies have demonstrated that Brugia malayi TRP-2 is activated by diethylcarbamazine. In this study, we heterologously expressed the Brugia malayi TRP-2b channel in the Human Embryonic Kidney (HEK) 293 cell line. Application of diethylcarbamazine to Bma-trp-2b transfected HEK293 cells leads to larger and more frequent increases in intracellular calcium compared to non-transfected cells. This increase can be inhibited using the TRPC specific antagonist SKF96365. Our study shows that diethylcarbamazine’s action is dependent upon the Brugia malayi TRP-2 channel and may also, in addition, activate endogenous mammalian TRP channels.