Endothelin-1 potentiates capsaicin-induced TRPV1 currents via the endothelin A receptor.
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Endothelin-1 potentiates capsaicin-induced TRPV1 currents via the endothelin A receptor. / Plant, Tim D; Zöllner, Christian; Mousa, Shaaban A; Oksche, Alexander.
In: EXP BIOL MED, Vol. 231, No. 6, 6, 2006, p. 1161-1164.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Endothelin-1 potentiates capsaicin-induced TRPV1 currents via the endothelin A receptor.
AU - Plant, Tim D
AU - Zöllner, Christian
AU - Mousa, Shaaban A
AU - Oksche, Alexander
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 231
SP - 1161
EP - 1164
JO - EXP BIOL MED
JF - EXP BIOL MED
SN - 1535-3702
IS - 6
M1 - 6
ER -