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KMID : 0811720170210050495
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Korean Journal of Physiology & Pharmacology
2017 Volume.21 No. 5 p.495 ~ p.507
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The activation of α2-adrenergic receptor in the spinal cord lowers sepsis-induced mortality
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Kim Sung-Su
Park Soo-Hyun
Lee Jae-Ryung
Jung Jun-Sub
Suh Hong-Won
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Abstract
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The effect of clonidine administered intrathecally (i.t.) on the mortality and the blood glucose level induced by sepsis was examined in mice. To produce sepsis, the mixture of D-galactosamine (GaLN; 0.6 g/10 ml)/lipopolysaccharide (LPS; 27 μg/27 μl) was treated intraperitoneally (i.p.). The i.t. pretreatment with clonidine (5 μg/5 μl) increased the blood glucose level and attenuated mortality induced by sepsis in a dose-dependent manner. The i.t. post-treatment with clonidine up to 3 h caused an elevation of the blood glucose level and protected sepsis-induced mortality, whereas clonidine post-treated at 6, 9, or 12 h did not affect. The pre-treatment with oral D-glucose for 30 min prior to i.t. post-treatment (6 h) with clonidine did not rescue sepsis-induced mortality. In addition, i.t. pretreatment with pertussis toxin (PTX) reduced clonidine-induced protection against mortality and clonidine-induced hyperglycemia, suggesting that protective effect against sepsis-induced mortality seems to be mediated via activating PTX-sensitive G-proteins in the spinal cord. Moreover, pretreatment with clonidine attenuated the plasma tumor necrosis factorα (TNF-α) induced by sepsis. Clonidine administered i.t. or i.p. increased p-AMPKα1 and p-AMPKα2, but decreased p-Tyk2 and p-mTOR levels in both control and sepsis groups, suggesting that the up-regulations of p-AMPKα1 and p-AMPKα2, or down-regulations of p-mTOR and p-Tyk2 may play critical roles for the protective effect of clonidine against sepsis-induced mortality.
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KEYWORD
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Blood glucose, Clonidine, p-AMPKα1, Sepsis, TNF-α, α2-adrenergic receptor
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