On the mechanism of histaminergic inhibition of glutamate release in the rat dentate gyrus
On the mechanism of histaminergic inhibition of glutamate release in the rat dentate gyrus
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DOI：
10.1111/j.1469-7793.1999.777ab.x
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发表时间：
1999-03-15
影响因子：
5.5
通讯作者：
Haas, HL
中科院分区：
文献类型：
--
作者：
Brown, RE;Haas, HL
1. 利用细胞外和全细胞膜片钳记录技术研究了大鼠齿状回兴奋性突触传递的组胺能抑制。组胺（10 μ M， 5分钟）抑制齿状回突触传递1小时。这种抑制作用被组胺h -3受体的选择性拮抗剂硫哌丁胺（10 μ M）阻断。组胺引起的抑郁程度与细胞外Ca2+浓度呈负相关。应用n型钙通道阻滞剂omega- concontoxin （0.5 μ M或1 μ M）或P/ q型钙通道阻滞剂omega-agatoxin （800 μ M）均不能阻止组胺抑制突触传递。钾通道阻滞剂4-氨基吡啶（4- ap, 100 μ M）增强了突触传递，降低了组胺（10 μ M）的抑制作用，4- ap对2 mM细胞外钙的抑制作用大于4 mM细胞外钙。组胺（10 μ M）不影响微型兴奋性突触后电流（mEPSCs）的振幅，仅对其频率有很小的影响。丝氨酸/苏氨酸蛋白激酶抑制剂H7 （100 μ M）和酪氨酸激酶抑制剂Lavendust in A （10 μ M）均不能阻断组胺能抑制。应用腺苷（20 μ M）或腺苷A(1)激动剂n -6-环戊基腺苷（CPA, 0.3 μ M）完全阻断组胺（10 μ M）的作用。我们得出结论，组胺作用于组胺H-3受体，通过g蛋白介导的多种钙通道的直接抑制，抑制突触前钙的进入，从而抑制谷氨酸释放。组胺H-3受体和腺苷A(1)受体共同作用于一个最终效应引起突触前抑制。
1. Histaminergic depression of excitatory synaptic transmission in the rat dentate gyrus was investigated using extracellular and whole-cell patch-clamp recording techniques in vitro.2. Application of histamine (10 mu M, 5 min) depressed synaptic transmission in the dentate gyrus for 1 h. This depression was blocked by the selective antagonist of histamine H-3 receptors, thioperamide (10 mu M).3.The magnitude of the depression caused by histamine was inversely related to the extracellular Ca2+ concentration. Application of the N-type calcium channel blocker omega-conotoxin (0.5 or 1 mu M) or the P/Q-type calcium channel blocker omega-agatoxin (800 nM) did not prevent depression of synaptic transmission by histamine.4. The potassium channel blocker 4-aminopyridine (4-AP, 100 mu M) enhanced synaptic transmission and reduced the depressant effect of histamine (10 mu M). 4-AP reduced the effect of histamine more in 2 mM extracellular calcium than in 4 mM extracellular calcium.5. Histamine (10 mu M) did not affect the amplitude of miniature excitatory postsynaptic currents (mEPSCs) and had only a small effect on their frequency.6. Histaminergic depression was not blocked by an inhibitor of serine/threonine protein kinases, H7 (100 mu M), or by an inhibitor of tyrosine kinases, Lavendust in A (10 mu M).7. Application of adenosine (20 mu M) or the adenosine A(1) agonist N-6-cyclopentyladenosine (CPA, 0.3 mu M) completely occluded the effect of histamine (10 mu M).We conclude that histamine, acting on histamine H-3 receptors, inhibits glutamate release by inhibiting presynaptic calcium entry via a direct G-protein-mediated inhibition of multiple calcium channels. Histamine H-3 receptors and adenosine A(1) receptors act upon a common final effector to cause presynaptic inhibition.