5-hydroxytryptamine and

B.-M. Eriksson and B.-A. Persson, Determination of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in plasma by direct injection in coupled-column liquid clrromatography with electrochemical detection , 7. Chromatogr. 459 351-360 (1988). 

After an overview of neurotransmitter systems and function and a consideration of which substances can be classified as neurotransmitters, section A deals with their release, effects on neuronal excitability and receptor interaction. The synaptic physiology and pharmacology and possible brain function of each neurotransmitter is then covered in some detail (section B). Special attention is given to acetylcholine, glutamate, GABA, noradrenaline, dopamine, 5-hydroxytryptamine and the peptides but the purines, histamine, steroids and nitric oxide are not forgotten and there is a brief overview of appropriate basic pharmacology. 

Sanders-Bush, E. Bushing, J.A. and Sulser, F. Long-term effects of p-chloroamphetamine on tryptophan hydroxylase activity and on levels of 5-hydroxytryptamine and 5-hydroxyindole aeetie acid in brain. 

Figure 2 Selective electrochemical detection of a mixture on multielectrode amper-ometry. AA = Ascorbic acid, NE = norepinephrine, DOPAC = 3-4-dihydroxy-phenylacetic acid, E = epinephrine bitartrate, 5-HIAA = 5-hydroxyindole-3-acetic acid, HVA = homovanillic acid, TRP = tryptophan, 5-HT = 5-hydroxytryptamine, and 3-MT = 3-methoxytyramine (separated by RPLC). Detection was with a 4-electrode glassy carbon array, with electrode 1 at 500 m V) electrode 2 at 700 mV, electrode 3 at 900 mV, and electrode 4 at 1100 mV. Note that at electrode 1, HVA, TRP, and 3-MT are not seen. At electrode 2, only TRP is not seen. A standard calomel electrode was used as reference. (Reprinted with permission from Hoogvliet, J. C., Reijn, J. M., and van Bennekom, W. P., Anal. Chem., 63, 2418, 1991. 1991 Analytical Chemistry.)...

Randic, M., and Yu, H. H. (1976) Effects of 5-hydroxytryptamine and bradykinin in cat dorsal horn neurones activated by noxious stimuli. Brain Res., 111 197-203. 

Gervasini G, Martinez C, Agundez JA, Garcia-Gamito FJ, Benitez J. 2001. Inhibition of cytochrome P450 2C9 activity in vitro by 5-hydroxytryptamine and adrenaline. Pharmacogenetics 11 29-37. 

Hows ME, Lacroix L, Heidbreder C, Organ AJ, Shah AJ. 2004. High-performance liquid chromatography/tandem mass spectrometric assay for the simultaneous measurement of dopamine, norepinephrine, 5-hydroxytryptamine and cocaine in biological samples. J Neurosci Methods 138 123. Hows ME, Organ AJ, Murray S, Dawson LA, Foxton R, et al. 

Parent M, Bush D, Rauw G, Master S, Vaccarino F, et al. 2001. Analysis of amino acids and catecholamines, 5-hydroxytryptamine and their metabolites in brain areas in the rat using in vivo microdialysis. Methods 23(1) 11-20. 

Figure 13.28 A possible mechanism by which increased levels of tryptophan and/or tyrosine can occur in neurones and lead to fatigue. The mechanism proposes that physical activity increases the entry of tryptophan or tyrosine into the neurones which increases the concentration of the neurotransmitters, 5-hydroxy-tryptamine or dopamine, respectively. The neurotransmitters are present in vesicles in the presynaptic terminal (Chapter 14). (The pathways for the formation of 5-hydroxytryptamine and dopamine are described in Chapter 14.) This enhances the amount release into the synapses which decreases the excitation of 5-hydroxytryptamine or dopamine neurones in the motor control pathway. It is assumed that they are inhibitory neurotransmitters, they will reduce electrical activity in the motor control pathway and hence nervous stimulation of muscle fibres. This results in fatigue. Mechanisms by which physical activity might result in increased entry of these amino acids into the brain are presented in Appendix 13.5.

Kirby LG, Chou-Green JM, Davis K, Lucki I (1997) The effects of different stressors on extracellular 5-hydroxytryptamine and 5-hydroxyindoleacetic acid. Brain Res 760 218-230 Kirby LG, Rice KC, Valentino RJ (2000) Effects of corticotropin-releasing factor on neuronal activity in the serotonergic dorsal raphe nucleus. Neuropsychopharmacology 22 148-162 Kozicz T, Yanaihara H, Arimura A (1998) Distribution of urocortin-like immunoreactivity in the central nervous system of the rat. J Comp Neurol 391 1-10 Lavicky J, Dunn AJ (1993) Corticotropin-releasing factor stimulates catecholamine release in hypothalamus and prefrontal cortex in freely moving rats as assessedby microdialysis. J Neurochem 60 602-612... 

Baker GB, Reynolds GP Biogenic amines and their metabolites in Alzheimer s disease noradrenaline, 5-hydroxytryptamine and 5-hydroxy indole-3-acetic acid depleted in hippocampus but not in substantia innominata. Neurosci Lett 100 335-339, 1989... 

Nicholson AN, Pascoe PA 5-Hydroxytryptamine and noradrenaline uptake inhibition studies on sleep in man. Neuropharmacology 25 1079-1083, 1986 Nicholson AN, Pascoe PA Studies on the modulation of the sleep-wakefulness continuum in man by fluoxetine, a 5-HT uptake inhibitor. Neuropharmacology 27 597-602, 1988... 

Ogren S-O, Ross SB, Holm AC, et al 5-Hydroxytryptamine and avoidance performance in the rat antagonism of the acute effect of p-chloroamphetamine by zimetidine, an inhibitor of 5-hydroxytryptamine uptake. Neurosci Lett 7 331-336, 1977... 

Serotonin has an effect on the hypothalamic control of pituitary function (see chapter 5), in central thermoregulation (attributed to the 5-HTj receptor), and in pain perception (probably the S-HTj receptor), where increased serotonergic function potentiates opiate analgesia. The administration of 5-HT reuptake inhibitors like fluoxetine increases the anorectic effect of 5-hydroxytryptamine and induces a selective suppression of nonprotein caloric intake in rats. The involvement of serotonin in endogenous psychiatric depression has been mentioned. 

Figure 30-28 Serotonin (5-hydroxytryptamine) and some drugs that affect receptors and transporters.

Quercetin also inhibited rat aortic contractions induced by noradrenaline, 5-hydroxytryptamine, and caffeine in Ca2+ -free media [110]. PMA enhanced this transient contraction elicited by noradrenaline, an effect that was abolished by quercetin. Furthermore, quercetin or the PKC inhibitor staurosporine, had no effect on 45Ca2+ efflux under resting conditions or when stimulated by noradrenaline. So, the inhibitory effects of quercetin on phasic contractile response induced by receptor agonists in... 

Mansour, T.E. (1957) The effect of lysergic acid diethylamide, 5-hydroxytryptamine and related compounds on the liver fluke Fasciola hepatica. British journal of Pharmacology 12, 406-409. 

Ribeiro, P. and Webb, R.A. (1 984) The occurrence, synthesis and metabolism of 5-hydroxytryptamine and 5-hydroxytryptophan in the cestode Hymenolepis diminuta. Comparative Biochemistry and Physiology C 79, 159-164. 

Thompson, C.S. and Mettrick, D.F. (1989) The effects of 5-hydroxytryptamine and glutamate on muscle contraction in Flymenolepis diminuta (Cestoda). Canadian Journal of Zoology 67, 1257-1262. 

GOthert M, Duhrsen U (1979) Effects of 5-hydroxytryptamine and related compounds on the sympathetic nerves of the rabbit heart. Naunyn Schmiedebergs Arch Pharmacol 308 9-18 Gotti C, Zoli M, Clementi F (2006) Brain nicotinic acetylcholine receptors native subtypes and their relevance. Trends Pharmacol Sci 27 482-91 Grady SR, Meinerz NM, Cao J, Reynolds AM, Picciotto MR, Changeux JP, McIntosh JM, Marks MJ, Collins AC (2001) Nicotinic agonists stimulate acetylcholine release from mouse interpeduncular nucleus a function mediated by a different nAChR than dopamine release from striatum. J Neurochem 76 258-68... 

Yusuf S, Al-Saady N, Camm AJ. 5-Hydroxytryptamine and atrial fibrillation how significant is this piece in the puzzle J Cardiovasc Electrophysiol 2003 14(2) 209-214. 

Differential scanning calorimetry has also been used to study the interaction of DPPC liposomes with the neuromediators norepinephrine and 5-hydroxytryptamine and four antidepressant drugs (imipramine, indalpine, citalopram, and milnacipran) known to inhibit uptake of these neurotransmitters [39]. Changes in the thermograms, transition temperature maximum, Tt, and ATt were determined as a function... 

The HPLC method described here allows the assay of both isoforms in the same run by using 5-hydroxytryptamine and 3-methoxy-4-hydroxybenzyl-amine as highly selective substrates for the A and B isoforms, respectively. The product of 5-hydroxytryptamine that is quantitated is 5-hydroxyindole-2-carboxylic acid, which is obtained by including aldehyde dehydrogenase in the assay mixture to oxidize the intermediate aldehyde. The product of monoamine oxidase B is 3-methoxy-4-hydroxybenzaldehyde. The internal standards used are 5-hydroxyindole-2-carboxylic acid and 3,4-dihydroxyben-zoic acid. 

Substrates (p-octopamine, dopamine, or 5-hydroxytryptamine) were separated from their N-acetylated products on an Ultrasphere I.P. C18 column (4.6 mm x 250 mm, 5 pm). The mobile phase was comprised of 75 mAf monobasic sodium phosphate, 1 pAf EDTA, 0.35 mAf 1-octanesulfonate (sodium salt), 11% methanol, and 4% acetonitrile. Coulometric detection was used. Detection of p-octopamine and its N-acetylated product was achieved at a potential of +0.75 V, while dopamine, 5-hydroxytryptamine and their products were detected at +0.50 V. 

Apart from the relatively small amounts that are required for synthesis of the neurotransmitter serotonin (5-hydroxytryptamine), and for net new protein synthesis, essentially the whole of the dietary intake of tryptophan is metabolized by way of the oxidative pathway shown in Figures 8.4 and 9.4, which provides both a mechanism for total catabolism by way of acetyl coenzyme A and a pathway for synthesis of the nicotinamide nucleotide coenzymes (Section 8.3). 

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