Norepinephrine functions

Dopamine, norepinephrine, and epinephrine (adrenalin) are biologically active amines that are collectively termed catecholamines. Dopamine and norepinephrine function as neurotransmitters in the brain and the autonomic nervous system. Norepinephrine and epinephrine are also synthesized in the adrenal medulla. 

Aston-Jones, G. Cohen, J. D. (2005b). An integrative theory of locus coeruleus-norepinephrine function Adaptive gain and optimal performance. Armu. Rev. Neurosci., 28, 403-450. 

The primary purpose of the endocrine system is to maintain homeostasis — that is, to maintain a relatively constant internal environment in the face of a constantly changing external environment. The endocrine system consists of hormones and the glands and tissues that produce the hormones. A hormone is a chemical substance released by certain cells to effect the function of other distant cells (endocrine function). Many compounds act as endocrine hormones as well as having paracrine and autocrine functions. Paracrine and autocrine describe actions on nearby cells and on other cells that produce the substance, respectively. There is considerable overlap between substances classified as hormones and other chemical messengers such as neurotransmitters and cytokines. Many substances function in more than one of these categories. For example, epinephrine and norepinephrine function as both neurotransmitters and adrenal medullary hormones. 

Wang YM, Xu F, Gainetdinov RR, Caron MG. 1999. Genetic approaches to studying norepinephrine function knockout of the mouse norepinephrine transporter gene. Biol. Psychiatry 46 1124-30... 

Norepinephrine functions biologically as a nenrotransmitter, transmitting a signal from one nenron to another neuron or muscle cell. After release from a neuron, norepinephrine diffuses through the tiny space between the cells (the synapse), where it can bind to a receptor protein on the surface of a nearby cell. Nerve impulses are typically short-lasting because the nenrotransmitter dissociates from its receptor. Once this happens, the neurotransmitter can quickly be chemically altered or transported into another cell, either of these terminating the nerve impulse. 

Distinctions among these classes of regulators are somewhat indefinite. Catecholamines, such as epinephrine and norepinephrine, function both as neurotransmitters and as hormones, depending upon their sites of synthesis and release. 

Biogenic amines. A general term usually used to describe endogenous amine-containing compounds such as dopamine, 5-hydroxy-tryptamine, and norepinephrine that function as neurotransmitters. 

Norepinephrine. An endogenous catecholamine that functions as a neurotransmitter. 

The original monoamine hypothesis of depression states that depressions are associated with a deficiency of catecholamines, particularly norepinephrine, at functionally important adrenergic receptor sites in the brain. Elation conversely may be associated with an excess of such amines. The hypothesis was articulated in 1966 only after the mechanism of action of the tricyclic antidepressant desipramine and of the psychostimulants... 

Another theory for the action of stimulant diugs in ADHD involves effects on nonstiiatal monoamine systems. Frontal cortical dopamine, norepinephrine, and serotonin are clearly important in cognitive functioning and impulse control. These neurotransmitters directly modulate reward-related behaviors associated with the striatal dopamine system. Moreover, the amygdala may be pharmacologically influenced leading to enhanced... 

Studies have now started to clarify the role of histamine Hi and H2 receptors in the cardiovascular manifestations of anaphylaxis. However, histamine can activate H3 and H4 receptors [56, 57]. Levi and coworkers [58-60] identified H3 receptors as inhibitory heteroreceptors in cardiac adrenergic nerve endings. This suggests a mechanism by which endogenous histamine can activate norepinephrine release in normal and ischemic conditions [61,62]. The functional identification ofH3 receptors in the human heart [59] means that these receptors might be directly and/or indirectly involved in the cardiovascular manifestations of anaphylactic reactions. 

Important products derived from amino acids include heme, purines, pyrimidines, hormones, neurotransmitters, and biologically active peptides. In addition, many proteins contain amino acids that have been modified for a specific function such as binding calcium or as intermediates that serve to stabilize proteins—generally structural proteins—by subsequent covalent cross-hnk-ing. The amino acid residues in those proteins serve as precursors for these modified residues. Small peptides or peptide-like molecules not synthesized on ribosomes fulfill specific functions in cells. Histamine plays a central role in many allergic reactions. Neurotransmitters derived from amino acids include y-aminobutyrate, 5-hydroxytryptamine (serotonin), dopamine, norepinephrine, and epinephrine. Many drugs used to treat neurologic and psychiatric conditions affect the metabolism of these neurotransmitters. 

McCormick, DA, Pape, HC and Williamson, A (1991) Actions of norepinephrine in the cerebral cortex and thalamus implications for function of the central noradrenergic system. Prog. Brain Res. 88 293-305. 

Povlock, SL and Amara, SG (1997) The structure and function of norepinephrine, dopamine and serotonin transporters. In Neurotransmitter Transporters Structure, Function, and Regulation (Ed. Reith, MEA), Humana Press, Totowa, NJ, pp. 1-28. 

These are four monoamines synthesized and seereted within many mammalian tissues, ineluding various regions in the brain, sympathetic nervous system, enlero-chromafhn cells of the digestive tract, and adrenal mednlla. These biogenic amines (indoleamine and catecholamines — dopamine, norepinephrine, and epinephrine) are synthesized within the cell from their precursor amino acids and have been associated with many physiological and behavioral functions in animals and humans. 

Another mechanism to maintain CO when contractility is low is to increase heart rate. This is achieved through sympathetic nervous system (SNS) activation and the agonist effect of norepinephrine on P-adrenergic receptors in the heart. Sympathetic activation also enhances contractility by increasing cytosolic calcium concentrations. SV is relatively fixed in HF, thus HR becomes the major determinant of CO. Although this mechanism increases CO acutely, the chronotropic and inotropic responses to sympathetic activation increase myocardial oxygen demand, worsen underlying ischemia, contribute to proarrhythmia, and further impair both systolic and diastolic function. 

Tricyclic antidepressants (TCAs) such as amitriptyline and doxepin have been used with some success in the treatment of IBS-related pain (Table 18-5). They modulate pain principally through their effect on neurotransmitter reuptake, especially norepinephrine and serotonin. Their helpfulness in functional gastrointestinal disorders seems independent of mood-altering effects normally associated with these agents. Low-dose TCAs (e.g., amitriptyline, desipramine, or doxepin 10 to 25 mg daily) may help patients with IBS who predominantly experience diarrhea or pain. 

O Classic views as to the cause of major depressive disorder focus on the monoamine neurotransmitters norepinephrine (NE), serotonin (5-HT), and to a lesser extent, dopamine (DA) in terms of both synaptic concentrations and receptor functioning. 

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