Catecholamines and Serotonin

Fig. I Chromatogram of catecholamines, serotonin and some metabolites together with creatinine A) examination at X = 365 nm, B) examination at A. = 254 nm.

Such events show how the immune, endocrine and central nervous systems are integrated in their responses to any form of stress. It is well established that physical or psychosocial stress causes increased secretions of prolactin, growth hormones, thyroid, and gonadal hormones, in addition to ACTH. Endogenous opioids are secreted under such conditions and function as immunomodulators, while also elevating the pain threshold. Receptors for such hormones exist on immunocompetent cells, along with receptors for catecholamines, serotonin and acetylcholine. 

Panholzer, T. J. Beyer, J. Lichtwald, K., Coupled-column liquid chromatographic analysis of catecholamines, serotonin, and metabolites in human urine, Clin. Chem. 1999, 45, 262-268... 

Methylation is an important reaction in the biosynthesis of endogenous compounds such as adrenaline and melatonin, in the inactivation of biogenic amines such as the catecholamines, serotonine and histamine, and in modulating the activities of macromolecules, such as proteins and nucleic acids. The number of xenobiotics that are methylated is comparatively modest, yet this reaction is seldom devoid of pharmacodynamic consequences (toxication or detoxication). Reactions of methylation imply the transfer of a methyl group from the onium-type cofactor S-adeno-sylmethionine (SAM) to the substrate by means of a methyltransferase. The activated methyl group from SAM is transferred to the acceptor molecules R — XH or RX, as shown in Fig. 31.30. 

Mefford, I. N., 1981, Application of HPLC with electrochemical detection to neurochemical analysis measurement of catecholamines, serotonin, and metabolites in rat brain, /. Neurosci. Meth. 3 207-224. 

These diseases are not detected via conventional screening methodology (i.e. organic acids, amino acids etc.), therefore diagnosis relies on the analysis of neurotransmitters and their metabolites in CSF, urine or plasma. In general, TH deficiency leads to low levels of catecholamines and their metabolites, AADC deficiency leads to decreased concentrations of catecholamines, serotonin and their metabolites. In AADC deficiency there is also an accumulation of neurotransmitter precursors, namely 5-hydroxytrypto-phan, levodopa and its methylated derivative, 3-0-methyldopa. D)9H deficiency leads to decreased norepinephrine and an increase in dopamine, and MAO-A deficiency to an increase in the biogenic amines and their 0-methylated catabolites, and to a decrease in concentration of their deami-nated catabolites. 

Baumgarten, H.G. Bjorklund, A. Lachenmayer, L. and Nobin, A. Evaluation of the effects of 5,7-dihydroxytryptamine on serotonin and catecholamine neurons in the rat CNS. Acta Physiol Scand [Suppl] 391 1-19, 1973. 

Histamine is synthesized in the brain from L-histidine by the enzyme histidine decarboxylase (HDC) (Fig. 2.2C). HDC can be inhibited by application of a-fluoromethylhistidine (a-FMH). Unlike serotonin and the catecholamines, no... 

Catecholamines and catechol Catecholamines catechol and serotonin Cu(II)-catalyzed luminol- H202 Phosphate buffer (pH 9.2) KMn04 in H2S04 Borate buffer (pH 9.5)... 

Sensitive electrochemical techniques have also been developed to directly measure the release of oxidizable neurotransmitters such as catecholamines (CAs) and serotonin (5-hydroxytryptamine, 5-HT). Current flows in the circuit when the potential of the electrode is positive enough to withdraw electrons from, i.e. oxidize, the released neurotransmitter. The technique is very sensitive and readily detects the release of individual quanta of neuro transmitter resulting from the fusion of single secretory vesicles to the plasmalemma (Fig. 10-2). 

In contrast to glutamate, y-aminobutyric acid (y-aminobutyrate, GABA) is an inhibitory compound. Metabolically derived from glutamate, GABA production illustrates a reaction, decarboxylation, common to the production of serotonin and the catecholamines (Figure 4.9). 

Several amino acids are broken down by de-carbo qflation. This reaction gives rise to what are known as biogenic amines, which have various functions. Some of them are components of biomolecules, such as ethanolamine in phospholipids (see p. 50). Cysteamine and T-alanine are components of coenzyme A (see p.l2) and of pantetheine (see pp. 108, 168). Other amines function as signaling substances. An important neurotransmitter derived from glutamate is y-aminobutyrate (GABA, see p.356). The transmitter dopamine is also a precursor for the catecholamines epinephrine and norepinephrine (see p.352). The biogenic amine serotonin, a substance that has many effects, is synthesized from tryptophan via the intermediate 5-hydroxytryptophan. 

Biogenic amines arise from amino acids by decarboxylation (see p. 62). This group includes 4-aminobutyrate (y-aminobutyric acid, GABA), which is formed from glutamate and is the most important inhibitory transmitter in the CNS. The catecholamines norepinephrine and epinephrine (see B), serotonin, which is derived from tryptophan, and histamine also belong to the biogenic amine group. All of them additionally act as hormones or mediators (see p. 380). 

Reserpine causes a breakdown of norepinephrine, dopamine, and serotonin in neuron endings. It weakens intracellular uptake of biogenic amines and reduces the ability if storing them in vesicles. It is possible that reserpine acts on membrane vesicles, irreversibly inhibiting ATP-Mg (adenosinetriphosphate) requiring process that is responsible for the uptake of biogenic amines in intemeuronal vesicles. Breakdown of catecholamines is expressed by a decreased number of intraneuronal serotonin and dopamine. 

These data and findings from serotonin depletion studies show that, in patients treated successfully, NA and serotonin systems are involved in maintenance of drug-induced remission. However, the absence of an increased severity in depressive symptoms in drug-free patients with depression suggests that alterations in serotonin and catecholamine release may not be causally involved in the pathophysiology of mood disorders. 

Nicholson AN, Pascoe PA Monoaminergic transmission and sleep in man, in Serotonin, Sleep and Mental Disorder. Edited by Idzikowski C, Cowen PJ. Petersfield, England, Wrightson Biomedical Publishing, 1991, pp 215-226 Nicholson AN, Pascoe PA, Stone BM Modulation of catecholamine transmission and sleep in man. Neuropharmacology 25 271-274, 1986 Nicholson AN, Pascoe PA, Turner C Modulation of sleep by trimipramine in man. Eur J Pharmacol 37 145-150, 1989a... 

---