Inhibition of TRPM8 function by the prostacyclin receptor requires coupling to Gq/11 proteins.
Prostacyclin
TRPM8
inflammatory pain
prostacyclin receptor
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
03 Dec 2023
03 Dec 2023
Historique:
revised:
16
11
2023
received:
18
04
2023
accepted:
21
11
2023
medline:
4
12
2023
pubmed:
4
12
2023
entrez:
4
12
2023
Statut:
aheadofprint
Résumé
The Transient Receptor Potential Melastatin subtype 8 (TRPM8) receptor-channel is involved in innocuous cold sensing and has a potent anti-inflammatory action. Its activation by lower temperature or chemical agonists such as menthol and icilin induces analgesic effects, reversing hypersensitivity and reducing chronic pain. On the other hand, prostacyclin (PGI We employed transient expression of human TRPM8 and IP-R in HEK293T cells and performed intracellular calcium and cAMP measurements. Additionally, we cultured neurons from the dorsal root ganglia (DRGs) of mice and determined the increase in intracellular calcium triggered by the TRPM8 agonist, icilin, in the presence of the IP-R agonist, cicaprost, the IP-R antagonist, CAY10441 and the Gq/11 inhibitor YM254890. Our results demonstrate that the activation of IP-R by selective agonists, such as cicaprost, beraprost, and iloprost, inhibits TRPM8 independently of the Gs-cAMP pathway. The potent inhibition of TRPM8 by IP-R involves Gq/11 coupling of IP-R. These effects were also observed in neurons isolated from the DRGs of mice. Our results demonstrate that an unusual signaling pathway of IP-R, namely the coupling to Gq/11 proteins, inhibits TRPM8, which may contribute to a better understanding of the role of TRPM8 and IP-R in the regulation of pain and inflammation.
Sections du résumé
BACKGROUND AND PURPOSE
OBJECTIVE
The Transient Receptor Potential Melastatin subtype 8 (TRPM8) receptor-channel is involved in innocuous cold sensing and has a potent anti-inflammatory action. Its activation by lower temperature or chemical agonists such as menthol and icilin induces analgesic effects, reversing hypersensitivity and reducing chronic pain. On the other hand, prostacyclin (PGI
EXPERIMENTAL APPROACH
METHODS
We employed transient expression of human TRPM8 and IP-R in HEK293T cells and performed intracellular calcium and cAMP measurements. Additionally, we cultured neurons from the dorsal root ganglia (DRGs) of mice and determined the increase in intracellular calcium triggered by the TRPM8 agonist, icilin, in the presence of the IP-R agonist, cicaprost, the IP-R antagonist, CAY10441 and the Gq/11 inhibitor YM254890.
KEY RESULTS
RESULTS
Our results demonstrate that the activation of IP-R by selective agonists, such as cicaprost, beraprost, and iloprost, inhibits TRPM8 independently of the Gs-cAMP pathway. The potent inhibition of TRPM8 by IP-R involves Gq/11 coupling of IP-R. These effects were also observed in neurons isolated from the DRGs of mice.
CONCLUSIONS AND IMPLICATIONS
CONCLUSIONS
Our results demonstrate that an unusual signaling pathway of IP-R, namely the coupling to Gq/11 proteins, inhibits TRPM8, which may contribute to a better understanding of the role of TRPM8 and IP-R in the regulation of pain and inflammation.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
This article is protected by copyright. All rights reserved.