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Tacrolimus, a calcineurin inhibitor, promotes capsaicin-induced colonic pain in mice
- Source :
- Journal of Pharmacological Sciences, Vol 143, Iss 1, Pp 60-63 (2020)
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- TRPV1 is phosphorylated and functionally upregulated by protein kinases, and negatively regulated by phosphatases including calcineurin. Since the clinical use of calcineurin-inhibiting immunosuppressants is commonly associated with chronic diarrhea, we examined if tacrolimus, a calcineurin inhibitor, promotes TRPV1-dependent colonic hypersensitivity in mice. Intracolonic administration of capsaicin, a TRPV1 agonist, caused referred hyperalgesia in the lower abdomen, an effect prevented by capsazepine, a TRPV1 blocker. Tacrolimus accelerated the intracolonic capsaicin-induced referred hyperalgesia. Similarly, intracolonic capsaicin caused spinal ERK phosphorylation, a marker for nociceptor excitation, an effect promoted by tacrolimus. Thus, tacrolimus may aggravate TRPV1-related colonic pain accompanying irritable bowel syndrome. Keywords: Tacrolimus, Colonic pain, TRPV1
- Subjects :
- Therapeutics. Pharmacology
RM1-950
Subjects
Details
- Language :
- English
- ISSN :
- 13478613
- Volume :
- 143
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Journal of Pharmacological Sciences
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.8cafb701d11c4db2a5001fff0e488fee
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.jphs.2020.01.006