Korean J Physiol Pharmacol.  2017 Sep;21(5):495-507. 10.4196/kjpp.2017.21.5.495.

The activation of α₂-adrenergic receptor in the spinal cord lowers sepsis-induced mortality

• Kim SS
• Park SH
• Lee JR
• Jung JS
• Suh HW

• KMID: 2388695
• DOI: http://doi.org/10.4196/kjpp.2017.21.5.495

Abstract

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 factor α (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.

Keyword

Blood glucose; Clonidine; p-AMPKα1; Sepsis; TNF-α; α₂-adrenergic receptor

MeSH Terms

Animals
Blood Glucose
Clonidine
Glucose
GTP-Binding Proteins
Hyperglycemia
Mice
Mortality*
Pertussis Toxin
Plasma
Sepsis
Spinal Cord*
Tumor Necrosis Factor-alpha
Blood Glucose
Clonidine
GTP-Binding Proteins
Glucose
Pertussis Toxin
Tumor Necrosis Factor-alpha