Endothelin-1 potentiates capsaicin-induced TRPV1 currents via the endothelin A receptor

• Published in: Experimental biology and medicine (Maywood, N.J.) Vol. 231; no. 6; p. 1161
• Main Authors: Plant, Tim D, Zöllner, Christian, Mousa, Shaaban A, Oksche, Alexander
• Format: Journal Article
• Language: English
• Published: England 01-06-2006
• Subjects: Capsaicin - pharmacology; Cell Line; Drug Synergism; Endothelin-1 - pharmacology; Humans; Immunohistochemistry; Patch-Clamp Techniques; Receptor, Endothelin A - metabolism; Recombinant Fusion Proteins - metabolism; Transfection; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism
• ISSN: 1535-3702
• DOI: 10.3181/00379727-232-2311161

Endothelin-1 (ET-1) both stimulates nociceptors and sensitizes them to painful stimuli. The cellular mechanisms of the ET-1-mediated effects are only poorly understood. TRPV1, the heat-, proton-, and capsaicin-sensitive cation channel already known to be modulated by a number of cellular mediators released by painful stimuli and during inflammation, is a potential target for the action of ET-1. In immunocytochemistry of rat lumbar dorsal root ganglion using TRPV1- and ET(A) receptor-specific antibodies, both proteins were found to be co-expressed in small sensory neurons. To provide evidence that ET-1 can modulate TRPV1 activity via the ET(A) receptor, we used HEK 293 cells transiently co-expressing a fusion protein of TRPV1 and the yellow fluorescent protein (TRPV1-YFP) and the ET(A) receptor. In whole-cell patch clamp recordings of HEK293 cells co-expressing TRPV1-YFP and the ET(A) receptor, capsaicin (10 nM) elicited small currents, which were markedly potentiated when capsaicin (10 nM) and ET-1 (100 nM) were applied simultaneously. The data indicate that ET-1 potentiates TRPV1 activity via the ET(A) receptor and that this process is likely to play a crucial role in the pain-producing and pain-potentiating effects of ET-1. Thus, ET(A) receptor antagonists may be of importance in painful states with increased circulating ET-1 levels, as found in cancer and in chronic inflammation.