Rebola Nelson, Coelho Joana E, Costenla Ana Rita, Lopes Luísa V, Parada António, Oliveira Catarina R, Soares-da-Silva Patrício, de Mendonça Alexandre, Cunha Rodrigo A
Center for Neuroscience of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal.
Eur J Neurosci. 2003 Aug;18(4):820-8. doi: 10.1046/j.1460-9568.2003.02815.x.
Adenosine is a neuromodulator that has been proposed to be a major endogenous anticonvulsant acting via A1 receptors. We tested if implementation of kindling through stimulation of the amygdala affected A1 receptor-mediated neuromodulation in hippocampal slices taken from rats 4 weeks after the last stage 5 seizure. The A1 receptor agonist, N6-cyclopentyladenosine (CPA) (6-100 nm), inhibited field excitatory postsynaptic potential (fEPSP) slope with an EC50 of 19.1-19.5 nm in control and sham-operated rats, but was less potent in kindled rats (EC50 = 42.7 nm). This might result from a decreased number of A1 receptors in hippocampal nerve terminal membranes, because A1 receptor immunoreactivity decreased by 28 +/- 3% and the binding density of the A1 receptor agonist [3H]R-PIA decreased from 1702 +/- 64 to 962 +/- 78 fmol/mg protein in kindled compared with control rats. The tonic inhibition of hippocampal synaptic transmission by endogenous adenosine was also lower in kindled rats, because A1 receptor blockade with 50 nm 1,3-dipropyl-8-cyclopentyladenosine (DPCPX) enhanced fEPSP slope by 23 +/- 3% and theta-burst-induced long-term potentiation by 94 +/- 4% in control rats but was virtually devoid of effects in kindled rats. The evoked release of adenosine from hippocampal slices or nerve terminals was 56-71% lower in kindled rats probably due to the combined decrease in the capacity of adenosine transporters and decreased release of adenosine 5'-triphosphate (ATP), which was partially compensated by a higher extracellular catabolism of ATP into adenosine in kindled rats. These results indicate that, although adenosine might inhibit the onset of epileptogenesis, once kindling is installed, the efficiency of the adenosine inhibitory system is impaired.
腺苷是一种神经调质，有人提出它是通过A1受体起作用的主要内源性抗惊厥剂。我们测试了通过刺激杏仁核进行点燃是否会影响取自末次5期癫痫发作4周后的大鼠海马切片中A1受体介导的神经调节。在对照大鼠和假手术大鼠中，A1受体激动剂N6-环戊基腺苷（CPA）（6 - 100纳米）抑制场兴奋性突触后电位（fEPSP）斜率，其半数有效浓度（EC50）为19.1 - 19.5纳米，但在点燃大鼠中效力较低（EC50 = 42.7纳米）。这可能是由于海马神经终末膜中A1受体数量减少，因为与对照大鼠相比，点燃大鼠中A1受体免疫反应性降低了28±3%，A1受体激动剂[3H]R-PIA的结合密度从1702±64降至962±78飞摩尔/毫克蛋白。内源性腺苷对海马突触传递的强直抑制在点燃大鼠中也较低，因为在对照大鼠中，用50纳米的1,3 - 二丙基 - 8 - 环戊基腺苷（DPCPX）阻断A1受体可使fEPSP斜率增加23±3%，使θ波爆发诱导的长时程增强增加94±4%，但在点燃大鼠中几乎没有作用。点燃大鼠中海马切片或神经终末诱发的腺苷释放降低了56 - 71%，这可能是由于腺苷转运体能力的联合下降以及腺苷5'-三磷酸（ATP）释放减少，而在点燃大鼠中ATP向腺苷的细胞外分解代谢增加部分补偿了这一情况。这些结果表明，尽管腺苷可能抑制癫痫发生的起始，但一旦点燃形成，腺苷抑制系统的效率就会受损。
