Neuropeptide kyotorphin impacts on lipopolysaccharide-induced glucocorticoid-mediated inflammatory response : a molecular link to nociception, neuroprotection, and anti-inflammatory action

Perazzo, Juliana; Lima, Carla; Heras, Montserrat; Bardají, Eduard; Ferreira, Mônica Lopes; Castanho, Miguel A. R. B.

http://hdl.handle.net/10451/32603

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Authors

Ferreira, Mônica Lopes

Castanho, Miguel A. R. B.

Abstract(s)

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