Nitric oxide synthase-independent long-term potentiation in area CA1 of hippocampus.
In order to elucidate the role of NO in LTP, we have investigated a biochemical effector of NO action at hippocampal synapses, guanylyl cyclase. We have observed that LTP-inducing stimuli elicit an increase in the activity of guanylyl cyclase, an effect blocked by inhibitors of NO synthase. Extracellular application of hemoglobin, which binds NO and thereby blocks its actions, also attenuated the increase in guanylyl cyclase activity. Taken together, these results provide direct biochemical evidence for an elevation of NO levels with LTP-inducing stimulation, and support the hypothesis that NO can function as a transcellular messenger in the hippocampus. These findings also implicate guanylyl cyclase as a target of NO and demonstrate that while NO is elevated with LTP-inducing stimuli, the activity of NO synthase is not necessary for induction of LTP by all stimulus paradigms.
Chetkovich
D M
DM
Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030.
Klann
E
E
Sweatt
J D
JD
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D004558:Electric Stimulation; D004594:Electrophysiology; D004789:Enzyme Activation / Q000502:physiology; D006162:Guanylate Cyclase / Q000378:metabolism; D006454:Hemoglobins / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000494:pharmacology; D009602:Nitrosamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D006454:Hemoglobins; D007211:Indoles; D009602:Nitrosamines; D016194:Receptors, N-Methyl-D-Aspartate; D009599:Nitroprusside; D015763:2-Amino-5-phosphonovalerate; C036246:N-nitroso-N-methyl-3-aminomethylindole; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006162:Guanylate Cyclase; D006152:Cyclic GMP