Neuropeptide kyotorphin impacts on lipopolysaccharide-induced glucocorticoid-mediated inflammatory response: a molecular link to nociception, neuroprotection, and anti-inflammatory action
ACS Chem. Neurosci.
; 8(8): 1663-1667, 2017.
Article
in En
| SES-SP, SESSP-IBPROD, SES-SP
| ID: but-ib15093
Responsible library:
BR78.1
Localization: BR78.1
ABSTRACT
Neuropeptide kyotorphin (KTP) is a potent analgesic if administered directly into the brain. In contrast, KTP-amide (KTP-NH2) is analgesic, neuroprotective, and anti-inflammatory following systemic administration, albeit its mechanism of action is unknown. The aim of this study was to shed light on the mechanism of action of KTP-NH2 at the molecular level. KTP-NH2 does not inhibit the enkephalinases angiotensin-converting-enzyme and dipeptidyl-peptidase 3. Intravital microscopy showed that KTP-NH2 decreased the number of rolling leukocytes in a mouse model of inflammation induced by lipopolysaccharide (LPS). Pretreatment with metyrapone abrogated the action of KTP-NH2. Interestingly, stimulating rolling leukocytes using CXCL-1 is also counteracted by the KTP-NH2, but this effect is not abrogated by metyrapone. We conclude that KTP-NH2 has dual action a glucocorticoid-mediated action, which is dominant in the full-fledged LPS-induced inflammation model, and a glucocorticoid-independent mechanism, which is predominant in models in which leukocyte rolling is stimulated but inflammation is not totally developed.
Full text:
1
Collection:
06-national
/
BR
Database:
SES-SP
/
SESSP-IBPROD
Language:
En
Journal:
ACS Chem. Neurosci.
Year:
2017
Document type:
Article