Effects of tiletamine on the adenosine monophosphate-activated protein kinase signaling pathway in the rat central nervous system.
OBJECTIVE
The dissociative anesthetic tiletamine, which acts on the central nervous system (CNS), is widely used in veterinary medicine and animal experiments. Recent studies indicate that adenosine 5'-monophosphate activated protein kinase (AMPK) plays a key role in the analgesic action of tiletamine. In the present study, the effects of tiletamine on the AMPK signaling pathway in rats were investigated.


METHODS
Sprague-Dawley rats were injected intraperitoneally with tiletamine and executed at 10, 20, 40 and 60min post injection. The cerebral cortex, hippocampus, thalamus, cerebellum and brainstem were immediately taken out to evaluate the mRNA and protein phosphorylation levels of liver kinase B1 (LKB1), AMPKα and eIF4E-binding protein 1 (4EBP1) using quantitative real-time polymerase chain reaction and western blot analysis.


RESULTS
Tiletamine increased AMPK mRNA expression in the rat brain (P<0.01). Increased mRNA expression of AMPK was accompanied by an increase in phosphorylation of LKB1, resulting in significant decreases in the phosphorylation levels of 4EBP1 in the corresponding brain regions (P<0.01).


CONCLUSIONS
In summary, the findings indicate that tiletamine regulates the mRNA expression and protein phosphorylation levels of LKB1, AMPK and 4EBP1 in the CNS, suggesting that the analgesic effect of the anesthetic is mediated, at least in part, by the AMPK signaling pathway.
College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province, China.
Li-Xue
LX
Su
College of Veterinary Medicine, Shandong Agricultural University, Taian, Shandong Province, China.
Xing-Xing
XX
Shi
College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province, China.
Peng
P
Yang
College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province, China.
Hao
H
Chen
College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province, China.
Xin
X
Li
College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province, China.
Hong-Gang
HG
Fan
College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province, China. Electronic address: hbwang1940@163.com.
Hong-Bin
HB
Wang
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000249:Adenosine Monophosphate; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013992:Tiletamine / Q000494:pharmacology*
D000778:Anesthetics, Dissociative; D012333:RNA, Messenger; D013992:Tiletamine; D000249:Adenosine Monophosphate; D055372:AMP-Activated Protein Kinases
AMPK; Analgesia; Rat brain; Tiletamine