The activation of α₂-adrenergic receptor in the spinal cord lowers sepsis-induced mortality.
10.4196/kjpp.2017.21.5.495
- Author:
Sung Su KIM
1
;
Soo Hyun PARK
;
Jae Ryung LEE
;
Jun Sub JUNG
;
Hong Won SUH
Author Information
1. Department of Pharmacology, Institute of Natural Medicine, College of Medicine Hallym University, Chuncheon 24252, Korea. hwsuh@hallym.ac.kr
- Publication Type:Original Article
- Keywords:
Blood glucose;
Clonidine;
p-AMPKα1;
Sepsis;
TNF-α;
α₂-adrenergic receptor
- MeSH:
Animals;
Blood Glucose;
Clonidine;
Glucose;
GTP-Binding Proteins;
Hyperglycemia;
Mice;
Mortality*;
Pertussis Toxin;
Plasma;
Sepsis;
Spinal Cord*;
Tumor Necrosis Factor-alpha
- From:The Korean Journal of Physiology and Pharmacology
2017;21(5):495-507
- CountryRepublic of Korea
- Language:English
-
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.
