5-Hydroxytryptamine release

Berger, U.V., Gu, X.F., Azmitia, E.C. The substituted amphetamines 3,4-methylenedioxymethamphet-amine, methamphetamine, p-chloroamphetamine and fenfluramine induce 5-hydroxytryptamine release via a common mechanism blocked by fluoxetine and cocaine. Eur. J. Pharmacol. 215 153, 1992. 

Kimura, Y., Okuda, H., and Arichi, S. (1988). Effects of various ginseng saponins on 5-hydroxytryptamine release and aggregation in human platelets. /. Pharm. Pharmacol. 40, 838-843. 

Inoue S, Kita T, Yamanaka T, Ogawa Y, Nakashima T, et al. 2002. Measurement of 5-hydroxytryptamine release in the rat medial vestibular nucleus using in vivo microdialysis. Neurosci Lett 323(3) 234-238. 

Ramirez-Latorre J, Yu CR, Qu X, Perin F, Karhn A, Role L (1996) Functional contributions of alpha5 subunit to neuronal acetylchohne receptor channels. Nature 380 347-351 Rasmussen BA, Perry DC (2006) An autoradiographic analysis of [ l]alpha-bungarotoxin binding in rat brain after chronic nicotine exposure. Neurosci Lett 404 9-14 Reuben M, Clarke PB (2000) Nicotine-evoked [ H]5-hydroxytryptamine release from rat striatal synaptosomes. Neuropharmacology 39 290-299... 

Raiteri, M., Maura, G., Folghera, S., et a/. Modulation of 5-hydroxytryptamine release by presynaptic inhibitory alpha 2-adrenoceptors in the human cerebral cortex. Naumn-Schmiedehergs Arch. Pharmacol. 342(5), 508-512. 1990. 

Schworer, H., Katsoulis, S., Racke, K., 1992. Histamine inhibits 5-hydroxytryptamine release from the porcine small intestine involvement of H3 receptors. Gastroenterology 102, 1906-1912. 

Sharp T, Bramwell SR, Grahame-Smith DG. 5-HTj agonists reduce 5-hydroxytryptamine release in rat hippocampus in vivo as determined by brain microdialysis. Br J Pharmacol 1993 96 283-290. 

Lawrence AJ, Marsden CA. Terminal autoreceptor control of 5-hydroxytryptamine release as measured by in vivo microdialysis in the conscious guinea-pig. J Neu-rochem 1992 58 142-146. 

The compound [ la(Z),2, 5a]-methyl-7-[2-(4-morpholinyl)-3-oxo-5-(phenyl-methoxy)cyclopentyl]-5-heptenoate (AH 19437) inhibited platelet aggregation and 5-hydroxytryptamine release without inhibiting fatty acid cyclo-oxygenase, thromboxane synthetase, cAMP phosphodiesterase or prostacyclin synthetase, consistent with the view that AH 19437 is a selective antagonist of platelet TXAj receptors [254-256],... 

Conti, J., Strope, E., Adams, R. N., and Marsden, C. A., 1978, Voltammetry in brain tissue chronic recording of stimulated dopamine and 5-hydroxytryptamine release. Life Sci. 23 2705-2716. 

Marsden, C. A., Bennett, G. W., Brazell, M., Sharp, T., and Stolz, J. F., 1981, Electrochemical monitoring of 5-hydroxytryptamine release in vitro and related in vivo measurements of indoleamines,/. Physiol. (Paris), 77 333-337. 

Inflammation is a non-specific reaction which can be induced by a variety of agents apart fiom microorganisms. Lymphokines and derivatives of arachidonic acid, including prostaglandins, leukotrienes and thromboxanes are probable mediators of the inflammatory response. The release of vasoactive amines such as histamine and serotonin (5-hydroxytryptamine) firm activated or damaged cells also contribute to inflammation. 

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. 

Hetey, L. and Quirling, K., Synaptosomal uptake and release of dopamine and 5-hydroxytryptamine in the nucleus accumbens in vitro following in vivo administration of lysergic acid diethlamide in rats, Acta Biol. Med. Ger., 39, 889, 1980. 

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). 

Another proposed mechanism of byssinosis is pharmacologic mediator release, especially histamine and 5-hydroxytryptamine (5-HT). Studies of histamine release following cotton dust exposure are complicated by the fact that cotton Itself contains histamine (98), the majority of which is found in the dust particle fraction below 20 P size (99). 

Westfall TC, Grant H, Perry H (1983) Release of dopamine and 5-hydroxytryptamine from rat striatal slices following activation of nicotinic chohnergic receptors, Gen Pharmacol 14 321-325 Wilson SJ, Sayette MA, Fiez JA (2004) Prefrontal responses to drug cues a neurocognitive analysis, Nat Neurosci 7 211-214... 

This hypothesis, similarly, proposes that physical activity increases tryptophan transport into the presynaptic neurone, where it is used to synthesise 5-hydroxytryptamine. Hence, when the nerve is stimulated, more 5-hydroxytryptamine is released into the synapse and, if this is another inhibitory transmitter in the motor control pathway, it will inhibit contraction (Figure 13.28). This is one of several effects of 5-hydroxytryptamine in the brain which are probably achieved via different receptors on different neurones. All three hypotheses are summarised in Figure 13.29. 

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.

Certain foods can trigger a migraine attack by effects on neurotransmitter release or metabolism in the brain. For example, a number of foods contain tryptamine which is known to cause release of other amines (dopamine, noradrenaline and 5-hydroxytryptamine) from both nerve terminals and platelets. This release could initiate the sequence of events that results in the migraine attack. Elimination of such foods from the diet can decrease the number of headaches. Compounds that discourage platelet aggregation (e.g. aspirin) may prevent such attacks. 

Figure 17.37 Hay fever. Pollen grains bind to sensib sed mast cells which degranulate, releasing the active biochemicals that result in the allergic response. Serotonin is 5-hydroxytryptamine.

Dennis J. McKenna, X.-M. Guan, and A. T. Shulgin. "3,4-methyl-enedioxyamphetamine (MDA) analogues exhibit differential effects on synaptosomal release of 3H-dopamine and 3H-5-hydroxytryptamine." Pharmacology, Biochemistry, and Behavior 38 (1991) 505-12. 

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