In vivo NO/cGMP signalling in the hippocampus.
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.
Fedele
E
E
Department of Experimental Medicine, University of Genova, Italy.
Marchi
M
M
Raiteri
M
M
D000375:Aging / Q000378:metabolism; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D004827:Epilepsy / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D015398:Signal Transduction; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D009569:Nitric Oxide; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D006152:Cyclic GMP