Catecholamine neurotransmitters

Dopamine is a catecholamine neurotransmitter in the CNS and at some ganglia in the autonomic nervous system. To date, three main types of receptors have been found D1( D2, and D3. The main dopaminergic systems in the brain are the nigro-neostriatal... 

Dopamine A catecholamine neurotransmitter, involved in mesolimbic reward and other important neural pathways. 

Noradrenaline A catecholamine neurotransmitter also known as norepinephrine. 

For each anatomic site listed, select the catecholamine neurotransmitter found in the highest amounts. 

It blocks reuptake of catecholamine neurotransmitters and causes a depletion of brain dopamine. 

An ECD measures the current generated by electroactive analytes in the HPLC eluent between electrodes in the flow cell. It offers sensitive detection (pg levels) of catecholamines, neurotransmitters, sugars, glycoproteins, and compounds containing phenolic, hydroxyl, amino, diazo, or nitro functional groups. The detector can be the amperometric, pulsed-amperometric, or coulometric type, with the electrodes made from vitreous or glassy carbon, silver, gold, or platinum, operated in the oxidative or reductive mode. Manufacturers include BSA, ESA, and Shimadzu. 

Dopamine is a major catecholamine neurotransmitter in the central nervous system (37) that is involved in the neuroregulation of locomotor activity, emotion, and neuroendocrine secretion (38,39). Clinically, dopaminergic drugs are used to treat Parkinson s disease and schizophrenia by activating or blocking dopamine receptors, respectively (40). 

The methyl transferases (MTs) catalyze the methyl conjugation of a number of small molecules, such as drugs, hormones, and neurotransmitters, but they are also responsible for the methylation of such macromolecules as proteins, RNA, and DNA. A representative reaction of this type is shown in Figure 4.1. Most of the MTs use S-adenosyl-L-methionine (SAM) as the methyl donor, and this compound is now being used as a dietary supplement for the treatment of various conditions. Methylations typically occur at oxygen, nitrogen, or sulfur atoms on a molecule. For example, catechol-O-methyltransferase (COMT) is responsible for the biotransformation of catecholamine neurotransmitters such as dopamine and norepinephrine. A-methylation is a well established pathway for the metabolism of neurotransmitters, such as conversion of norepinephrine to epinephrine and methylation of nicotinamide and histamine. Possibly the most clinically relevant example of MT activity involves 5-methylation by the enzyme thiopurine me thy Itransf erase (TPMT). Patients who are low or lacking in TPMT (i.e., are polymorphic) are at... 

The sympathomimetic drugs are discussed in Chapter 10. In brief, the most commonly abused of these drugs, such as cocaine, work primarily as indirect agonists of the catecholamine neurotransmitter systems via inhibitory actions upon the transmitter reuptake system. Considerable evidence supports a role for dopamine in mediating the rewarding effects of cocaine. There is also evidence that blockade of serotonin uptake may contribute to cocaine s actions. 

Release. Certain drugs will increase synaptic activity by directly increasing the release of neurotransmitter from the presynaptic terminal. Amphetamines appear to exert their effects on the CNS primarily by increasing the presynaptic release of catecholamine neurotransmitters (e.g., norepinephrine). Conversely, other compounds may inhibit the synapse by directly decreasing the amount of transmitter released during each action potential. An example is botulinum toxin (Botox), which can be used as a skeletal muscle relaxant because of its ability to impair the release of acetylcholine from the skeletal neuromuscular junction (see Chapter 13). 

Catecholamine neurotransmitters are subsequently inactivated by enzymic methylation of the 3-hydroxyl (via catechol-O-methyltransferase) or by oxidative removal of the amine group via monoamine oxidase. Monoamine oxidase inhibitors are sometimes used to treat depression, and these drugs cause an accumulation of amine neurotransmitters. Under such drug treatment, simple amines such as tyramine in cheese, beans, fish, and yeast extracts are also not metabolized and can cause dangerous potentiation of neurotransmitter activity. 

In vivo tolerance to copper is quite high, however, deficiency and excess are serious problems. Infants are particularly vulnerable as they take time to assimilate the correct levels and it is known that trace copper from cooking utensils or water pipes can cause childhood cirrhosis. Copper deficiency leads to arterial weakness and heart enlargement. This is probably caused by a decrease in catecholamine neurotransmitters derived from the biosynthesis of adrenaline which requires the copper-containing enzymes phenylalanine hydroxylase, dopamine P-monooxygenase and tyrosinase. 

Despite the surge of genetic studies in schizophrenia, few have examined genes in relation to the deficit syndrome. One gene that has received some attention is the catechol-O-methyltransferase (COMT) gene. COMT is an enzyme involved in the metabolism of catecholamine neurotransmitters. In the general... 

Catechol O-methyltransferase plays an important role in the catabolism of catecholamine neurotransmitters such as dopamine, norepinephrine, and epinephrine, and inactivation of catechol estrogens and catechol xenobiotics. Several different methods have been developed. 

Transamination and Oxidative Deamination Catalyzed by Di-hydroxyphenylalanine (DOPA) Decarboxylase DOPA decarboxylase catalyzes the decarboxylation of dihydroxyphenylalanine to yield dopamine (and hence the other catecholamine neurotransmitters see Figure 13.4) and... 

Cytosolic Ca can modulate the activity of serine/threonine CaMKs via calmodulin. For instance, neuronal CaMK stimulates phosphorylation and activates tyrosine hydroxylase, the limiting enzyme in the synthesis of catecholamine neurotransmitters. Ca also regulates the activation of the conventional PKC isoforms. Increased Ca " promotes binding of Ca " to... 

Similarly, the cyclic voltammograms of catecholamine neurotransmitters dopamine (DA), norepinephrine (NE) and epinephrine (EP) on bare and gold nanoparticle-modified ITO electrodes were measured and are illustrated in Figure 8. As can be seen, the voltammetric responses of DA, NE and EP are significantly improved on a gold nanoparticle-modified ITO electrode compared with bare ITO. 

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