Functional Vanilloid Receptor VR1 Is Expressed on Megakaryocytes and Platelets, and Acts as a Sensor for Hypertheimia Generating Endocannabinoids.

Recent investigations have been revealing that platelet can sense shear stress and cold stimulation. These mechanical and physical stimuli alter the platelet functions, including induction of activation and irreversible dysfunction. These data may suggest that platelets, most small-sized cells, can efficiently circulate in the microcirculatory vasculature, and can sense the peripheral physical conditions including temperature.

Here we show that human megakaryocytic cell line, MEG-01 and platelets express vanilloid receptor VR1, a receptor for capsaicin. It has been identified that VR1 is linked to thermal sensor, and this can sense hyperthermia around 43 °. Therefore we examined the physiological significance of VR1 expressed on MEG-01 and platelets.

First we identified the expression of VR1 on human platelets and MEG-01 by immunoblotting, flowcytometer and RT-PCR, and identified the expression of VR1 on these cells. Hyperthermia stimulation of MEG-01 at 40–43 ° generated a endocannabinoids, 2-arachidonylglycerol(2-AG) and anandamide. Since this effect of hyperthermia stimulation was abolished by the incubation with capsazepine, an antagonistic analogue of capsaicin, it was suggested that the effect of hyperthermia might through VR1. It is well known that 2-AG and anandamide act on their specific receptors, CB1, CB2 and VR1 expressed on various cell-types, and act as an endocannabinoids, and accomplish diverse physiological functions, including vessel dilatation. Hyperthermia stimulation also affected the cell-cycle and induced G1-phase arrest in MEG-01 cells, partially through autocrine manner of generated endocannabinoids by acting of CB1 and CB2 receptors. Moreover prolonged hyperthermia stimulation up to 6 hours induced cellular apoptosis in MEG-01 by releasing cytocrome C and resulting caspase cascade activation.

Based on these results, we hypothesize that VR1 on platelets may act as a hyperthermal sensor and generate endocannabinoid, and this may regulate the diverse systems including vessel functions.