Pharmacological inhibition of TRPV2 attenuates phagocytosis and lipopolysaccharide-induced migration of primary macrophages.

Background And Purpose: In macrophages, transient receptor potential vanilloid 2 (TRPV2) channel contributes to various cellular processes such as cytokine production, differentiation, phagocytosis and migration. Due to a lack of selective pharmacological tools, its function in immunological processes is not well understood and the identification of novel and selective TRPV2 modulators is highly desirable.

Experimental Approach: Novel and selective TRPV2 modulators were identified by screening a compound library using Ca influx assays with human embryonic kidney 293 (HEK293) cells heterologously expressing rat TRPV2.

Valdecoxib blocks rat TRPV2 channels.

The transient receptor potential vanilloid 2 (TRPV2) channel is broadly expressed in a multitude of different tissues and is implicated in the pathology of several diseases, such as the progression of different cancer types. However, a lack of specific, potent and non-toxic TRPV2 activators and inhibitors complicate further studies to clarify the role of TRPV2. We here present valdecoxib as a novel inhibitor of heterologously expressed rat TRPV2 channels in HEK293 cells and native TRPV2 channels, endogenously expressed in the rat basophilic leukemia (RBL-2H3) cell line.

Fluorescent analogs of peptoid-based HDAC inhibitors: Synthesis, biological activity and cellular uptake kinetics.

Fluorescent tagging of bioactive molecules is a powerful tool to study cellular uptake kinetics and is considered as an attractive alternative to radioligands. In this study, we developed fluorescent histone deacetylase (HDAC) inhibitors and investigated their biological activity and cellular uptake kinetics. Our approach was to introduce a dansyl group as a fluorophore in the solvent-exposed cap region of the HDAC inhibitor pharmacophore model.