Monoamine neurotransmitter

Norepinephrine is a monoamine neurotransmitter

Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group that is connected to an aromatic ring by a two-carbon chain (-CH2-CH2-). All monoamines are derived from aromatic amino acids like phenylalanine, tyrosine, tryptophan, and the thyroid hormones by the action of aromatic amino acid decarboxylase enzymes. Monoaminergic systems, i.e., the networks of neurons that utilize monoamine neurotransmitters, are involved in the regulation of cognitive processes such as emotion, arousal, and certain types of memory. It has been found that monoamine neurotransmitters play an important role in the secretion and production of neurotrophin-3 by astrocytes, a chemical which maintains neuron integrity and provides neurons with trophic support.[1] Drugs used to increase (or reduce) the effect of monoamine are sometimes used to treat patients with psychiatric disorders, including depression, anxiety, and schizophrenia.[2]

Examples

Biosynthetic pathways for catecholamines and trace amines in the human brain[3][4][5]
Graphic of trace amine and catecholamine metabolism
The image above contains clickable links
Phenethylaminergic trace amines and the catecholamines are derivatives of L-phenylalanine.
Classical monoamines
Trace amines

Specific transporter proteins called monoamine transporters that transport monoamines in or out of a cell exist. These are the dopamine transporter (DAT), serotonin transporter (SERT), and the norepinephrine transporter (NET) in the outer cell membrane and the vesicular monoamine transporter (VMAT1 and VMAT2) in the membrane of intracellular vesicles.

After release into the synaptic cleft, monoamine neurotransmitter action is ended by reuptake into the presynaptic terminal. There, they can be repackaged into synaptic vesicles or degraded by the enzyme monoamine oxidase (MAO), which is a target of monoamine oxidase inhibitors, a class of antidepressants.

Evolution

A phylogenetic tree showing how a number of monoamine receptors are related to each other.

As demonstrated by the wide existence of monoamine transmitters, an organism's ability to modify its behavior is advantageous to its survival. This system is found in various species such as nematodes, lobsters, desert locusts, hens, mice and zebra finches.[11]

Disorders

Disorders of monoamine neurotransmitters exist, part of a growing number of neurotransmitter disorders identified. Such disorders are responsible for biosynthesis degradation and difficulty in transporting neurotransmitters such as dopamine, norepinephrine, epinephrine, or serotonin. Monoamine neurotransmitter disorders mimic the symptoms of other more prevalent neurological disorders (e.g. cerebral palsy) and thus are frequently misdiagnosed.[2]

See also

References

  1. ↑ Mele, Tina; Čarman-Kržan, Marija; Jurič, Damijana Mojca (2010). "Regulatory role of monoamine neurotransmitters in astrocytic NT-3 synthesis". International Journal of Developmental Neuroscience. 28 (1): 13–9. doi:10.1016/j.ijdevneu.2009.10.003. PMID 19854260.
  2. 1 2 Kurian, Manju A; Gissen, Paul; Smith, Martin; Heales, Simon JR; Clayton, Peter T (2011). "The monoamine neurotransmitter disorders: An expanding range of neurological syndromes". The Lancet Neurology. 10 (8): 721–33. doi:10.1016/S1474-4422(11)70141-7. PMID 21777827.
  3. ↑ Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines". Pharmacol. Ther. 125 (3): 363–375. doi:10.1016/j.pharmthera.2009.11.005. PMID 19948186.
  4. ↑ Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends Pharmacol. Sci. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID 15860375.
  5. ↑ Wang X, Li J, Dong G, Yue J (February 2014). "The endogenous substrates of brain CYP2D". Eur. J. Pharmacol. 724: 211–218. doi:10.1016/j.ejphar.2013.12.025. PMID 24374199. The highest level of brain CYP2D activity was found in the substantia nigra (Bromek et al., 2010). The in vitro and in vivo studies have shown the contribution of the alternative CYP2D-mediated dopamine synthesis to the concentration of this neurotransmitter although the classic biosynthetic route to dopamine from tyrosine is active. CYP2D6 protein level is approximately 40% lower in the frontal cortex, cerebellum, and hippocampus in PD patients, even when controlling for CYP2D6 genotype (Mann et al., 2012). ... Tyramine levels are especially high in the basal ganglia and limbic system, which are thought to be related to individual behavior and emotion (Yu et al., 2003c). Studies have demonstrated that dopamine is formed from p-tyramine as well as m-tyramine via tyramine 3-hydroxylation or 4-hydroxylation by rat CYP2D2, 2D4, and 2D18 as well as human CYP2D6. ... Both rat CYP2D and human CYP2D6 have a higher affinity for m-tyramine compared with p-tyramine for the generation of dopamine. Rat CYP2D isoforms (2D2/2D4/2D18) are less efficient than human CYP2D6 for the generation of dopamine from p-tyramine. The Km values of the CYP2D isoforms are as follows: CYP2D6 (87–121 μm) ≈ CYP2D2 ≈ CYP2D18 > CYP2D4 (256 μm) for m-tyramine and CYP2D4 (433 μm) > CYP2D2 ≈ CYP2D6 > CYP2D18 (688 μm) for p-tyramine (Bromek et al., 2010; Thompson et al., 2000).
  6. ↑ Romero-Calderón R, Uhlenbrock G, Borycz J, Simon AF, Grygoruk A, Yee SK, Shyer A, Ackerson LC, Maidment NT, Meinertzhagen IA, Hovemann BT, Krantz DE (November 2008). "A glial variant of the vesicular monoamine transporter is required to store histamine in the Drosophila visual system". PLoS Genet. 4 (11): e1000245. doi:10.1371/journal.pgen.1000245. PMC 2570955Freely accessible. PMID 18989452. Unlike other monoamine neurotransmitters, the mechanism by which the brain's histamine content is regulated remains unclear. In mammals, vesicular monoamine transporters (VMATs) are expressed exclusively in neurons and mediate the storage of histamine and other monoamines.
  7. 1 2 3 4 5 6 7 Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines". Pharmacol. Ther. 125 (3): 363–375. doi:10.1016/j.pharmthera.2009.11.005. PMID 19948186. Trace amines are metabolized in the mammalian body via monoamine oxidase (MAO; EC 1.4.3.4) (Berry, 2004) (Fig. 2) ... It deaminates primary and secondary amines that are free in the neuronal cytoplasm but not those bound in storage vesicles of the sympathetic neurone ... Similarly, β-PEA would not be deaminated in the gut as it is a selective substrate for MAO-B which is not found in the gut ...
    Brain levels of endogenous trace amines are several hundred-fold below those for the classical neurotransmitters noradrenaline, dopamine and serotonin but their rates of synthesis are equivalent to those of noradrenaline and dopamine and they have a very rapid turnover rate (Berry, 2004). Endogenous extracellular tissue levels of trace amines measured in the brain are in the low nanomolar range. These low concentrations arise because of their very short half-life ...
  8. 1 2 3 Miller GM (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity". J. Neurochem. 116 (2): 164–176. doi:10.1111/j.1471-4159.2010.07109.x. PMC 3005101Freely accessible. PMID 21073468.
  9. 1 2 3 4 Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends Pharmacol. Sci. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID 15860375. In addition to the main metabolic pathway, TAs can also be converted by nonspecific N-methyltransferase (NMT) [22] and phenylethanolamine N-methyltransferase (PNMT) [23] to the corresponding secondary amines (e.g. synephrine [14], N-methylphenylethylamine and N-methyltyramine [15]), which display similar activities on TAAR1 (TA1) as their primary amine precursors...Both dopamine and 3-methoxytyramine, which do not undergo further N-methylation, are partial agonists of TAAR1 (TA1). ...
    The dysregulation of TA levels has been linked to several diseases, which highlights the corresponding members of the TAAR family as potential targets for drug development. In this article, we focus on the relevance of TAs and their receptors to nervous system-related disorders, namely schizophrenia and depression; however, TAs have also been linked to other diseases such as migraine, attention deficit hyperactivity disorder, substance abuse and eating disorders [7,8,36]. Clinical studies report increased β-PEA plasma levels in patients suffering from acute schizophrenia [37] and elevated urinary excretion of β-PEA in paranoid schizophrenics [38], which supports a role of TAs in schizophrenia. As a result of these studies, β-PEA has been referred to as the body’s ‘endogenous amphetamine’ [39]
  10. ↑ Wainscott DB, Little SP, Yin T, Tu Y, Rocco VP, He JX, Nelson DL (January 2007). "Pharmacologic characterization of the cloned human trace amine-associated receptor1 (TAAR1) and evidence for species differences with the rat TAAR1". The Journal of Pharmacology and Experimental Therapeutics. 320 (1): 475–85. doi:10.1124/jpet.106.112532. PMID 17038507.
  11. ↑ Lövheim, Hugo (2012). "A new three-dimensional model for emotions and monoamine neurotransmitters". Medical Hypotheses. 78 (2): 341–8. doi:10.1016/j.mehy.2011.11.016. PMID 22153577.

External links

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