This is the 2007 version. Click here for the 2017 chapter 02 table of contents.

Nitric Oxide, Glutamate, and Neuroimmunology

One of the most unexpected findings in modern neuroscience was that nitric oxide (NO) can function as a transmitter substance. Nobody expected a gas to be a transmitter, but it is...and it is broken down very rapidly after it is released, which is one reason nobody discovered it earlier.

Why was the discovery that NO worked as a transmitter unexpected?

Nitric oxide the transmitter is not to be confused with nitrous oxide (N20), the so-called "laughing gas" used by dentists as an anesthetic. The transmitter nitric oxide (NO) is a lighter gas with one unpaired electron. It reacts vigorously with other molecules, and it vanishes within 4 to 5 seconds in the presence of oxygen. After its discovery, nitric oxide was found to be involved in many important many that it was proclaimed "molecule of the year" by the journal Science in 1992.

Where is glutamate found, in a food additive? Is it rare or common, as a transmitter?

Glutamate is a neurotransmitter that interacts with nitrous oxide and often causes nitric oxide to be released. Glutamate is familiar to many people as an ingredient of monosodium glutamate (MSG), the flavor-enhancing food additive. Glutamate is neurotoxic (nerve-damaging) in large doses. However, in small doses, glutamate is common and important in the nervous system. Glutamate is released by about 90% of neurons during excitation (Magistretti, Pellerin, Rothman, & Shulman, 1999). The release of glutamate leads to a cascade of chemical events, including the consumption of glucose that is picked up on PET scans.

How has research into glutamate helped stroke victims?

As a transmitter, glutamate fits into receptor sites like the proverbial key into a lock. An important type of glutamate receptor is the NMDA receptor. Mild stimulation of the NMDA receptor results in learning and memory, but overstimulation of the NMDA receptor cause neurotoxicity or the killing of neurons. Some of the damaging after-effects of stroke and brain injury are due to excessive release of glutamate and the excessive activation of NMDA receptors. If glutamate release (or NMDA reception) can be suppressed after a brain injury, the extent of injury might be reduced.

There are indications that up to 70% of the cell death resulting from hypoxia (cut-off of oxygen due to a stroke) can be prevented if NMDA receptors are blocked (Helmuth, 2000). A new class of drugs, designed to do just this, is helping doctors treat stroke victims and minimize cell death from strokes. For a good discussion of this line of research, and the role of glutamate in cell death from stroke, see this URL:


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