Forghani R, Krnjević K
Anaesthesia Research Department, McGill University, Montréal, Québec, Canada.
Hippocampus. 1995;5(1):71-7. doi: 10.1002/hipo.450050109.
How adenosine leakage and tetanic release might affect long-term potentiation (LTP) was investigated by applying adenosine antagonists 8(p-sulfophenyl)theophylline (8SPT) or 8-cyclopentyl-3,7-dihydro-1,3-dipropyl-1H-purine-2,6-dione (DPCPX) to slices, while recording CA1 field EPSPs and population spikes. In the first series of experiments, we applied weak double tetani (at 100 Hz, for 1 s) that were subliminal for evoking LTP in initial control runs. In the presence of 8SPT--at concentrations (10-50 microM) which block both A1 and A2 receptors--the same tetani consistently evoked LTP of population spikes but not of excitatory postsynaptic potentials (EPSPs), whereas DPCPX (50 nM), which blocks only A1 receptors, facilitated LTP of both EPSPs and population spikes. These results are consistent with previous evidence that tetanic adenosine release on the one hand depresses LTP via A1 receptors but on the other facilitates LTP via A2 receptors. In a second set of experiments, 8SPT (50-100 microM) did not prevent the induction of LTP of both EPSPs and population spikes by stronger tetanic stimulation. Therefore A2 receptor activation is not essential for the induction of LTP when stronger tetani are applied. Overall, the main effect of endogenous adenosine release is to oppose LTP induction.
通过向脑片施加腺苷拮抗剂8-（对-磺苯基）茶碱（8SPT）或8-环戊基-3,7-二氢-1,3-二丙基-1H-嘌呤-2,6-二酮（DPCPX），同时记录CA1区场兴奋性突触后电位（EPSP）和群体峰电位，研究了腺苷泄漏和强直释放如何影响长时程增强（LTP）。在第一组实验中，我们施加了弱双强直刺激（100Hz，持续1秒），在初始对照实验中这种刺激强度低于引发LTP的阈值。在8SPT存在的情况下——其浓度为（10 - 50μM），可同时阻断A1和A2受体——相同的强直刺激始终能引发群体峰电位的LTP，但不能引发兴奋性突触后电位（EPSP）的LTP，而仅阻断A1受体的DPCPX（50 nM）则促进了EPSP和群体峰电位两者的LTP。这些结果与先前的证据一致，即强直刺激时腺苷释放一方面通过A1受体抑制LTP，但另一方面通过A2受体促进LTP。在第二组实验中，8SPT（50 - 100μM）并不能阻止更强的强直刺激诱导EPSP和群体峰电位的LTP。因此，当施加更强的强直刺激时，A2受体激活对于LTP的诱导并非必不可少。总体而言，内源性腺苷释放的主要作用是对抗LTP的诱导。
