Acetylsalicylic acid enhances tachyphylaxis of repetitive capsaicin responses in TRPV1-GFP expressing HEK293 cells.
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 μM 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 1μM ASA, a concentration much below the one needed to inhibit cyclooxygenase (IC50 of 35 μM in thromboxane B2 production assay). In contrast, calcium transients induced by a single stimulus of 0.3 or 1 μM capsaicin were not significantly reduced by 0.3 or 1 μM 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).
Department of Neurophysiology, Centre for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim of the University of Heidelberg, Ludolf-Krehl-Str.13-17, D-68167 Mannheim, Germany.
Kristina
K
Maurer
Department of Neurophysiology, Centre for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim of the University of Heidelberg, Ludolf-Krehl-Str.13-17, D-68167 Mannheim, Germany.
Uta
U
Binzen
Department of Neurophysiology, Centre for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim of the University of Heidelberg, Ludolf-Krehl-Str.13-17, D-68167 Mannheim, Germany.
Handan
H
Mörz
Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim of the University of Heidelberg, German Red Cross Blood Service of Baden-Württemberg-Hessen, Friedrich-Ebert-Straße 107, D-68167 Mannheim, Germany.
Peter
P
Bugert
Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim of the University of Heidelberg, German Red Cross Blood Service of Baden-Württemberg-Hessen, Friedrich-Ebert-Straße 107, D-68167 Mannheim, Germany.
Angelika
A
Schedel
Department of Neurophysiology, Centre for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim of the University of Heidelberg, Ludolf-Krehl-Str.13-17, D-68167 Mannheim, Germany.
Rolf-Detlef
RD
Treede
Department of Neurophysiology, Centre for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim of the University of Heidelberg, Ludolf-Krehl-Str.13-17, D-68167 Mannheim, Germany. Electronic address: wolfgang.greffrath@medma.uni-heidelberg.de.
Wolfgang
W
Greffrath
D000107:Acetylation; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D013618:Tachyphylaxis; D013929:Thromboxane B2 / Q000096:biosynthesis
D000700:Analgesics; D011993:Recombinant Fusion Proteins; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D049452:Green Fluorescent Proteins; D013929:Thromboxane B2; D051545:Cyclooxygenase 1; D001241:Aspirin; D002211:Capsaicin; D002118:Calcium
Acetylsalicylic acid; Calcium imaging; Cyclooxygenase (COX); MAPK/ERK