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Neuroscience Notes
A Miscellany
(revised 26 November 2000) 

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Glutamate  |  Nitric Oxide  |  Melatonin  | Dopamine  |


Glutamate is a major excitatory amino acid neurotransmitter accounting for an estimated forty percent of all nerve signals in the human brain, and involved in phenomena such as neural development, learning, and memory formation. Glutamate is ordinarily released under close cellular biochemical control and re-uptake, and in excess amounts it is an intense excitant of nerve cells and potentially toxic. Glutamate is suspected as an important contributor to the pathogenesis of a number of neurodegenerative disorders, including amyotrophic lateral sclerosis and parkinsonian dementia. The glutamate receptor is the molecular site that mediates the actions of glutamate neurotransmitters, and this receptor has been a focus of intensive research and has been differentiated into N-methyl D-aspartate (NMDA), kainate, and quisqualate subtypes. Neurons that release glutamate are called "glutamatergic", and they have been located in many important areas of the human brain.

Nitric Oxide

The gas nitric oxide belongs to an entirely new class of neurotransmitters discovered in the 1990s. In the brain, the enzyme that synthesizes nitric oxide (nitric oxide synthase) is localized in discrete populations of neurons. In the peripheral autonomic nervous system, the enzyme occurs in neurons that regulate the adrenal medulla, the posterior pituitary, and the smooth muscle cells of the intestine involved in peristalsis. In all of these systems, nitric oxide acts as a neurotransmitter released as a consequence of neural activity. Nitric oxide has also been implicated as a messenger in the response of macrophages (immune system cells) to cancer cells and invading bacteria. It is also released from endothelium in response to acetylcholine and other vasodilators, with a resultant relaxation of blood vessels, and is involved in penile erection. Nitric oxide is a free radical with a half-life of only a few seconds, and its concentration in tissues is difficult to establish quantitatively. It should not be confused with nitrous oxide ("laughing gas"), which is an analgesic gas used as an auxiliary in anesthesia in dentistry and surgery.



R.L. Sack (Science & Medicine Sep/Oct 1998) reviews the neurobiology and medical aspects of melatonin, and makes the following points: 1) The most important role of melatonin in all species is to provide a hormonal signal of night-time darkness. The secretion of the hormone is tightly controlled by the *circadian pacemaker. 2) Melatonin is a phylogenetically ancient hormone, found even in some single-cell organisms and in some plants. In lower vertebrates (e.g., reptiles), the pineal body lies close to the skin and is directly photosensitive: sunlight falling on the overlying skin inhibits melatonin production. In these species, the pineal body has been called a "third eye". In mammals, the pineal gland is deep within the skull and is not photosensitive. The timing of melatonin secretion in mammals is controlled by neural pathways: tracts from the retina of the eye to the *hypothalamus (retino-hypothalamic tract) and from the hypothalamus (suprachiasmatic *nucleus) to the pineal gland. The suprachiasmatic nucleus of the hypothalamus is the master circadian pacemaker in mammals, controlling the timing of most circadian rhythms, including core body temperature, *cortisol secretion, sleepiness, and melatonin secretion. 3) At the cellular level, melatonin receptors are members of the superfamily of *G protein-coupled receptors, which characteristically have 7 *transmembrane domains. Activation of these receptors inhibits *cyclic AMP production by the enzyme adenylyl cyclase. 4) The author suggests that as a therapeutic agent, melatonin can be useful in the treatment of certain sleep and mood disorders. The author suggests the basis for this is circadian phase-shifting and the release of accumulated sleep drive. 5) Concerning its use as a nutritional supplement, the author says, "Melatonin appears to be remarkably safe, at least for short-term use... The effects of long-term administration are not defined." Concerns have been raised about possible reproductive effects, but most studies have shown little or no effect on reproductive hormone levels. There are reports that melatonin modifies the *vasoconstriction response in rat arteries.
QY: Robert L. Sack, Oregon Health Sciences Univ. 503-494-2998.
Text Notes:
... ... *tryptophan: A nutritionally essential amino acid that serves as a precursor for many molecular entities of importance in the nervous system.
... ... *serotonin: (5-hydroxytryptamine, 5-HT) Synthesized from tryptophan. Acts as both a peripheral neurotransmitter in the gut and a central neurotransmitter in the brain.
... ... *circadian pacemaker: Many organisms exhibit daily (circadian) rhythms, cyclical variations in various bodily functions, metabolisms, etc., even in constant light or constant darkness. In simple organisms, the pacemakers are biochemical reaction loops; in higher organisms, complex signaling structures are involved in the rhythms.
... ... *hypothalamus: A deep brain structure with various clusters of nerve cells controlling several important homeostatic functions such as temperature regulation and food intake, and in addition the sex drive, aggressive emotions, psychosomatic effects, etc. The hypothalamus essentially integrates the activity of the autonomic nervous system, and it acts as an intermediary between the endocrine (hormone) system and the nervous system, with various hypothalamic neuron types secreting hormones themselves. In general, the term "hormones" refers to chemical messengers which are distributed systemically via the bloodstream.
... ... *nucleus: In this context, the term "nucleus" refers to a cluster of nerve cells involved in a particular neurological function.
... ... *cortisol: A corticosteroid hormone secreted by the adrenal gland.
... ... *G protein: G-proteins are a family of signal-coupling proteins that act as intermediaries between activated cell receptors and effectors, for example, the transduction of hormonal signals from the cell surface to the cell interior, and certain G-proteins are known to interact with adenylyl cyclase. The G-protein is apparently embedded in the cell membrane with parts exposed on the outside surface and inside surface. The outside moiety is activated by the first messenger, and the inside moiety activates the second messenger, the G-protein thus acting as a trans-membrane signal transducer.
... ... *transmembrane domains: A transmembrane domain is a segment of protein anchored in the plasma membrane bilayer. If one visualizes the protein as a long linear polymer, the polymer can be looped back and forth across the plasma membrane with different segments of the protein anchored in the membrane according to lipid solubility characteristics of the segments of the polymer chain.
... ... *cyclic AMP: ATP (adenosine triphosphate) is the most important chemical energy source in all living cells, intimately involved in various cell functions and cell metabolism, and an entity in numerous cyclic chemical pathways involved in the entity in numerous cyclic chemical pathways involved in the synthesis of components. One of the reaction products of ATP is cAMP (cyclic AMP, or adenosine 3,5-monophosphate), which acts as an intracellular hormone (i.e., a chemical messenger). Cyclic AMP is derived from ATP in a reaction catalyzed by the enzyme adenylyl cyclase (also called adenyl cyclase and adenylate cyclase). Cyclic AMP is called the second messenger; the first messenger is the hormone that interacts with its receptor on the cell surface.
... ... *vasoconstriction response: In general, the term vasoconstriction refers to a narrowing of blood vessels, which in higher organisms is under physiological control via various signaling systems. Vasoconstriction produces an increase in blood pressure, systemic or local, depending on the distribution of signals.


Dopamine and schizophrenia: Caesaren birth may be a factor in triggering schizophrenia. See Alison Motluk, Cruel to be kind (New Scientist 21 Nov 98) (external).

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