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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2009

Open Access 01-12-2009 | Research

Cellular localization of kinin B1 receptor in the spinal cord of streptozotocin-diabetic rats with a fluorescent [Nα-Bodipy]-des-Arg9-bradykinin

Authors: Sébastien Talbot, Patrick Théberge-Turmel, Dalinda Liazoghli, Jacques Sénécal, Pierrette Gaudreau, Réjean Couture

Published in: Journal of Neuroinflammation | Issue 1/2009

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Abstract

Background

The kinin B1 receptor (B1R) is upregulated by pro-inflammatory cytokines, bacterial endotoxins and hyperglycaemia-induced oxidative stress. In animal models of diabetes, it contributes to pain polyneuropathy. This study aims at defining the cellular localization of B1R in thoracic spinal cord of type 1 diabetic rats by confocal microscopy with the use of a fluorescent agonist, [Nα-Bodipy]-des-Arg9-BK (BdABK) and selective antibodies.

Methods

Diabetes was induced by streptozotocin (STZ; 65 mg/kg, i.p.). Four days post-STZ treatment, B1R expression was confirmed by quantitative real-time PCR and autoradiography. The B1R selectivity of BdABK was determined by assessing its ability to displace B1R [125I]-HPP-desArg10-Hoe140 and B2R [125I]-HPP-Hoe 140 radioligands. The in vivo activity of BdABK was also evaluated on thermal hyperalgesia.

Results

B1R was increased by 18-fold (mRNA) and 2.7-fold (binding sites) in the thoracic spinal cord of STZ-treated rats when compared to control. BdABK failed to displace the B2R radioligand but displaced the B1R radioligand (IC50 = 5.3 nM). In comparison, IC50 values of B1R selective antagonist R-715 and B1R agonist des-Arg9-BK were 4.3 nM and 19 nM, respectively. Intraperitoneal BdABK and des-Arg9-BK elicited dose-dependent thermal hyperalgesia in STZ-treated rats but not in control rats. The B1R fluorescent agonist was co-localized with immunomarkers of microglia, astrocytes and sensory C fibers in the spinal cord of STZ-treated rats.

Conclusion

The induction and up-regulation of B1R in glial and sensory cells of the spinal cord in STZ-diabetic rats reinforce the idea that kinin B1R is an important target for drug development in pain processes.
Appendix
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Metadata
Title
Cellular localization of kinin B1 receptor in the spinal cord of streptozotocin-diabetic rats with a fluorescent [Nα-Bodipy]-des-Arg9-bradykinin
Authors
Sébastien Talbot
Patrick Théberge-Turmel
Dalinda Liazoghli
Jacques Sénécal
Pierrette Gaudreau
Réjean Couture
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2009
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-6-11

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