Lysophosphatidic acid directly activates TRPV1 through a C-terminal binding site
Por:
Nieto-Posadas, A, Picazo-Juarez, G, Llorente, I, Jara-Oseguera, A, Morales-Lazaro, S, Escalante-Alcalde, D, Islas, LD, Rosenbaum, T
Publicada:
1 ene 2012
Resumen:
Since 1992, there has been growing evidence that the bioactive phospholipid lysophosphatidic acid (LPA), whose amounts are increased upon tissue injury, activates primary nociceptors resulting in neuropathic pain. The TRPV1 ion channel is expressed in primary afferent nociceptors and is activated by physical and chemical stimuli. Here we show that in control mice LPA produces acute pain-like behaviors, which are substantially reduced in Trpv1-null animals. Our data also demonstrate that LPA activates TRPV1 through a unique mechanism that is independent of G protein-coupled receptors, contrary to what has been widely shown for other ion channels, by directly interacting with the C terminus of the channel. We conclude that TRPV1 is a direct molecular target of the pain-producing molecule LPA and that this constitutes, to our knowledge, the first example of LPA binding directly to an ion channel to acutely regulate its function.
Filiaciones:
Nieto-Posadas, A:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Dept Neurodesarrollo & Fisiol, Mexico City 04510, DF, Mexico
Picazo-Juarez, G:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Dept Neurodesarrollo & Fisiol, Mexico City 04510, DF, Mexico
Llorente, I:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Dept Neurodesarrollo & Fisiol, Mexico City 04510, DF, Mexico
Jara-Oseguera, A:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Mexico City 04510, DF, Mexico
Morales-Lazaro, S:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Dept Neurodesarrollo & Fisiol, Mexico City 04510, DF, Mexico
Escalante-Alcalde, D:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Dept Neurodesarrollo & Fisiol, Mexico City 04510, DF, Mexico
Islas, LD:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Mexico City 04510, DF, Mexico
Rosenbaum, T:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Dept Neurodesarrollo & Fisiol, Mexico City 04510, DF, Mexico
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