INHIBITION OF ADENOSINE KINASE INCREASES ENDOGENOUS ADENOSINE AND DEPRESSES NEURONAL-ACTIVITY IN HIPPOCAMPAL SLICES

被引:118
作者
PAK, MA [1 ]
HAAS, HL [1 ]
DECKING, UKM [1 ]
SCHRADER, J [1 ]
机构
[1] UNIV DUSSELDORF,INST PHYSIOL 1 & 2,D-40001 DUSSELDORF,GERMANY
关键词
IODOTUBERCIDIN; EHNA; DPCPX; HIPPOCAMPAL SLICE; ADENOSINE RELEASE; ADENOSINE;
D O I
10.1016/0028-3908(94)90142-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Endogenous adenosine in the extracellular space inhibits neuronal activity. The roles of adenosine kinase, S-adenosylhomocysteine-hydrolase and adenosine deaminase activities in the regulation of the adenosine levels were investigated in rat hippocampal slices. Iodotubercidin, an inhibitor of adenosine kinase, added to the perfusion fluid at 5 mu M increased the release of adenosine from the slices more than 2-fold. Iodotubercidin treatment caused inhibition of population spike discharges and hyperpolarization of pyramidal cells, mimicking the effects of exogenously applied adenosine. Adenosine dialdehyde, an inhibitor of S-adenosylhomocysteine hydrolase, and erythro-9-(2-hydroxp-3-nonyl) adenine (EHNA), an inhibitor of adenosine deaminase had little or no effect on the parameters tested. The action of iodotubercidin was greater during deaminase inhibition. The A1-receptor antagonist DPCPX had actions opposite to those of adenosine and blocked the electrophysiological effects of exogenous adenosine and of iodotubercidin. Thus adenosine kinase activity is a significant factor in the regulation of adenosine levels in the hippocampus.
引用
收藏
页码:1049 / 1053
页数:5
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