Excitatory amino acid signal transduction in the hippocampus: role of noradrenergic afferents and nitric oxide in cGMP increases in vivo.
Previous studies have demonstrated that excitatory amino acid (EAA)-dependent increases in cerebellar cGMP are dependent upon the prior activation of nitric oxide (NO) synthase. Additionally, the actions of NMDA, but not kainate or quisqualate, in elevating cerebellar cGMP have been shown to be dependent upon intact noradrenergic innervation of the cerebellum. In the current study we extended these observations to the hippocampus and again found that EAA-dependent increases in hippocampal cGMP also involve prior formation of NO. And as in the case of the cerebellum, NMDA-dependent increases in hippocampal cGMP involve prior release of norepinephrine which in turn apparently activates an alpha 1-adrenergic receptor to elicit cGMP increases. In toto, these data suggest that a key role of NMDA receptors in these brain regions is to presynaptically regulate the release of norepinephrine, thereby modulating the tone of this monoaminergic system. This may be a general principle which needs experimentation in other terminal fields of noradrenergic pathways.
Wood
P L
PL
Hoechst Roussel Pharmaceuticals, Somerville, NJ 08876.
Ryan
R
R
Li
M
M
D000704:Analysis of Variance; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000502:physiology*
D009569:Nitric Oxide; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D006152:Cyclic GMP; D007608:Kainic Acid; D009638:Norepinephrine