Acetylsalicylic acid enhances tachyphylaxis of repetitive capsaicin responses in TRPV1-GFP expressing HEK293 cells

作者：Maurer Kristina; Binzen Uta; Moerz Handan; Bugert Peter; Schedel Angelika; Treede Rolf Detlef; Greffrath Wolfgang^*

来源：Neuroscience Letters, 2014, 563: 101-106.

DOI：10.1016/j.neulet.2014.01.050

• Acetylsalicylic acid
• Calcium imaging
• Cyclooxygenase (COX)
• MAPK/ERK

Since many years acetylsalicylic acid (ASA) is known for its antithrombotic, antiphlogistic and analgesic effects caused by irreversible acetylation of cyclooxygenase. ASA also inhibits capsaicin- and heat-induced responses in cultured dorsal root ganglia (DRG) neurons, suggesting TRPV1 (transient receptor potential channel of the vanilloid receptor family, subtype 1) to be an additional target of ASA. We now studied the effect of ASA on heterologously expressed rat TRPV1 using calcium microfluorimetry. Capsaicin dose-dependently increased intracellular calcium with an EC50 of 0.29 mu M in rTRPV1 expressing HEK293 cells. During repetitive stimulation the second response to capsaicin was reduced (53.4 +/- 8.3% compared to vehicle control; p < 0.005; Student's unpaired t-test) by 1 mu M ASA, a concentration much below the one needed to inhibit cyclooxygenase (IC50 of 35 mu M in thromboxane B2 production assay). In contrast, calcium transients induced by a single stimulus of 0.3 or 1 mu M capsaicin were not significantly reduced by 0.3 or 1 mu M ASA. These data suggest that ASA increases the tachyphylaxis of rTRPV1 channel activation. Mechanisms are unknown and may be direct by e.g. stabilization of the desensitized state or indirect via inhibition of intracellular signaling pathways e.g. of the mitogen-activated protein kinase family (MAPK/ERK).

• 出版日期2014-3-20