Optical Control of TRPM8 Channels with Photoswitchable Menthol.

Transient receptor potential melastatin 8 (TRPM8) channels are well known as sensors for cold temperatures and cooling agents such as menthol and icilin and these channels are tightly regulated by the membrane lipid phosphoinositol-4,5-bisphosphate (PIP). Since TRPM8 channels emerged as promising drug targets for treating pain, itching, obesity, cancer, dry eye disease, and inflammation, we aimed at developing a high-precision TRPM8 channel activator, to achieve spatiotemporal control of TRPM8 activity with light. In this study, we designed, synthesized and characterized the first photoswitchable TRPM8 activator azo-menthol (AzoM).

Helix 8 is the essential structural motif of mechanosensitive GPCRs.

G-protein coupled receptors (GPCRs) are versatile cellular sensors for chemical stimuli, but also serve as mechanosensors involved in various (patho)physiological settings like vascular regulation, cardiac hypertrophy and preeclampsia. However, the molecular mechanisms underlying mechanically induced GPCR activation have remained elusive. Here we show that mechanosensitive histamine H receptors (HRs) are endothelial sensors of fluid shear stress and contribute to flow-induced vasodilation.

Impact of Sensitization and Inflammation on the Interaction of Mast Cells With the Intestinal Epithelium in Rats.

The density of intestinal mast cells has been reported to increase during inflammatory bowel disease (IBD). As mast cell mediators are known to increase the permeability of epithelial tight junctions, we hypothesized that antigen responses in sensitized animals might be enhanced under inflammatory conditions. This would contribute to a vicious circle by further enhancing the entry of luminal antigens into the colonic wall and thereby continuing the inadequate immune response during IBD.

Expression of functional inhibitory neurotransmitter transporters GlyT1, GAT-1, and GAT-3 by astrocytes of inferior colliculus and hippocampus.

Neuronal inhibition is mediated by glycine and/or GABA. Inferior colliculus (IC) neurons receive glycinergic and GABAergic inputs, whereas inhibition in hippocampus (HC) predominantly relies on GABA. Astrocytes heterogeneously express neurotransmitter transporters and are expected to adapt to the local requirements regarding neurotransmitter homeostasis.