Effects of carnosine on amygdaloid-kindled seizures in Sprague-Dawley rats.
The effects of carnosine (beta-alanyl-L-histidine) on amygdaloid-kindled seizures were investigated in rats. I.p. injection of carnosine (500, 1000, 1500 mg/kg, i.p.) significantly decreased seizure stage, afterdischarge duration and generalized seizure duration, and significantly prolonged generalized seizure latency of amygdaloid-kindled seizures, in a dose-dependent, and time-related manner. The protective effect of carnosine (1500 mg/kg) was completely antagonized by histamine H1-antagonists pyrilamine (2, 5 mg/kg, i.p.) and diphenhydramine (5, 10 mg/kg, i.p.), but not by histamine H2-antagonist zolantidine even at a high dose of 10 mg/kg. Carnosine (1500 mg/kg, i.p.) caused a significant increase of carnosine and histidine levels in the hypothalamus, thalamus, hippocampus, amygdala and cortex, as well as histamine levels in the hippocampus and amygdala. I.c.v. injection of alpha-fluoromethylhistidine (50 microg, i.c.v.), a selective and irreversible histidine decarboxylase inhibitor, only partially reversed the inhibition of amygdaloid-kindled seizures induced by carnosine. In addition, carnosine significantly decreased glutamate contents in the amygdala and hippocampus. These results indicate that carnosine could protect against amygdaloid-kindled seizures in rats, and its action may be due to the activation of histamine postsynaptic H1-receptors via two different mechanisms, one being carnosine's direct action, and the other being indirectly mediated by histaminergic pathway. The study suggests that carnosine may be an endogenous anticonvulsant factor in the brain and could be used as a new antiepileptic drug in the future.
Jin
C-L
CL
Department of Pharmacology and Neurobiology, School of Medicine, Zhejiang University, Hangzhou, China 310031.
Yang
L-X
LX
Wu
X-H
XH
Li
Q
Q
Ding
M-P
MP
Fan
Y-Y
YY
Zhang
W-P
WP
Luo
J-H
JH
Chen
Z
Z
D000679:Amygdala / Q000473:pathology / Q000502:physiology*; D000818:Animals; D000927:Anticonvulsants; D002336:Carnosine / Q000378:metabolism / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006639:Histidine / Q000378:metabolism; D007276:Injections, Intraventricular; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D008762:Methylhistidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000473:pathology / Q000517:prevention & control*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D008762:Methylhistidines; D018698:Glutamic Acid; D006639:Histidine; D005680:gamma-Aminobutyric Acid; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D002336:Carnosine