The G protein-coupled receptor-transient receptor potential channel axis: molecular insights for targeting disorders of sensation and inflammation.
Pharmacol Rev
; 67(1): 36-73, 2015.
Article
en En
| MEDLINE
| ID: mdl-25361914
ABSTRACT
Sensory nerves are equipped with receptors and ion channels that allow them to detect and respond to diverse chemical, mechanical, and thermal stimuli. These sensory proteins include G protein-coupled receptors (GPCRs) and transient receptor potential (TRP) ion channels. A subclass of peptidergic sensory nerves express GPCRs and TRP channels that detect noxious, irritant, and inflammatory stimuli. Activation of these nerves triggers protective mechanisms that lead to withdrawal from danger (pain), removal of irritants (itch, cough), and resolution of infection (neurogenic inflammation). The GPCR-TRP axis is central to these mechanisms. Signals that emanate from the GPCR superfamily converge on the small TRP family, leading to channel sensitization and activation, which amplify pain, itch, cough, and neurogenic inflammation. Herein we discuss how GPCRs and TRP channels function independently and synergistically to excite sensory nerves that mediate noxious and irritant responses and inflammation in the skin and the gastrointestinal and respiratory systems. We discuss the signaling mechanisms that underlie the GPCR-TRP axis and evaluate how new information about the structure of GPCRs and TRP channels provides insights into their functional interactions. We propose that a deeper understanding of the GPCR-TRP axis may facilitate the development of more selective and effective therapies to treat dysregulated processes that underlie chronic pain, itch, cough, and inflammation.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Células Receptoras Sensoriales
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Transducción de Señal
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Trastornos de la Sensación
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Receptor Cross-Talk
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Receptores Acoplados a Proteínas G
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Canales de Potencial de Receptor Transitorio
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Inflamación
Límite:
Animals
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Humans
Idioma:
En
Revista:
Pharmacol Rev
Año:
2015
Tipo del documento:
Article