Fedele E, Marchi M, Raiteri M
Department of Experimental Medicine, University of Genova, Italy.
Neurochem Res. 2001 Sep;26(8-9):1069-78. doi: 10.1023/a:1012309223236.
In the hippocampus of freely-moving rats, basal extracellular levels of cGMP are inhibited by L-NARG or ODQ whereas they are increased by NO donors or phosphodiesterase inhibitors. Activation of NMDA receptors also augments cGMP dialysate levels in a MK-801 and L-NARG sensitive manner, an effect dramatically diminished during ageing. Experiments with AMPA, AMPA receptor antagonists and cyclothiazide revealed complex relationships with GABAergic circuits that potently control the NO/cGMP pathway. Furthermore, the activity of this neurochemical cascade is also modulated by hippocampal nicotinic receptors via enhancement of endogenous glutamate release and stimulation of NMDA receptors. From a behavioural point of view, increased hippocampal excitation leads to the appearance of epileptic-like manifestations that, however, seem unrelated to the increase of NO/cGMP formation.
在自由活动大鼠的海马体中，cGMP的基础细胞外水平受到L - NARG或ODQ的抑制，而NO供体或磷酸二酯酶抑制剂则使其升高。NMDA受体的激活也以对MK - 801和L - NARG敏感的方式增加cGMP透析液水平，这种效应在衰老过程中显著减弱。使用AMPA、AMPA受体拮抗剂和环噻嗪的实验揭示了与能有效控制NO/cGMP途径的GABA能回路的复杂关系。此外，海马体烟碱受体通过增强内源性谷氨酸释放和刺激NMDA受体，也对这种神经化学级联反应的活性进行调节。从行为学角度来看，海马体兴奋性增加会导致癫痫样表现的出现，然而，这似乎与NO/cGMP生成的增加无关。
