5-Hydroxytryptamine function

Rose JE, Levin ED (1991) Inter-relationships between conditioned and primary reinforcement in the maintenance of cigarette smoking. Br J Addict 86(5) 605-609 Rosecrans JA (1971) Elfects of nicotine on brain area 5-hydroxytryptamine function in male and female rats separated for differences of activity. Eur J Pharmacol 16(1) 123-127 Rosecrans JA (1972) Brain area nicotine levels in male and female rats with different levels of spontaneous activity. Neuropharmacology ll(6) 863-870 Rosecrans JA, Schechter MD (1972) Brain area nicotine levels in male and female rats of two strains. Arch Int Pharmacodyn Ther 196(l) 46-54 Saigusa T, Takada K, et al (1997) Dopamine efflux in the rat nucleus accumbens evoked by dopamine receptor stimulation in the entorhinal cortex is modulated by oestradiol and progesterone. Synapse 25(1) 37 3... 

Serotoninergic System. Figure 1 Graphical representation of the current classification of 5-hydroxytryptamine (5-HT) receptors. Receptor subtypes represented by shaded boxes and lowercase designate receptors that have not been demonstrated to definitively function in native systems. Abbreviations 3-5r cyclic adenosine monophosphate (cAMP) phospholipase C (PLC) negative (-ve) positive (+ve)... 

Tryptamine itself is found in all major centers of the brain. Its physiologic role in central nervous system (CNS) function, however, remains unclear. 5-Hydroxytryptamine (5-HT, serotonin) is an important neurotransmitter in the CNS. The structural similarity of the tryptamine-related hallucinogens with 5-HT presumably forms the neurochemical basis for their action within the CNS. 

Important products derived from amino acids include heme, purines, pyrimidines, hormones, neurotransmitters, and biologically active peptides. In addition, many proteins contain amino acids that have been modified for a specific function such as binding calcium or as intermediates that serve to stabilize proteins—generally structural proteins—by subsequent covalent cross-hnk-ing. The amino acid residues in those proteins serve as precursors for these modified residues. Small peptides or peptide-like molecules not synthesized on ribosomes fulfill specific functions in cells. Histamine plays a central role in many allergic reactions. Neurotransmitters derived from amino acids include y-aminobutyrate, 5-hydroxytryptamine (serotonin), dopamine, norepinephrine, and epinephrine. Many drugs used to treat neurologic and psychiatric conditions affect the metabolism of these neurotransmitters. 

HT3 receptor. 5-Hydroxytryptamine receptor a receptor for serotonin (a neurotransmitter), which activates a variety of second messenger signaling systems and through them indirectly regulates the function of ion channels. 

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. 

Enteric nerves control intestinal smooth muscle action and are connected to the brain by the autonomic nervous system. IBS is thought to result from dysregulation of this brain-gut axis. The enteric nervous system is composed of two gan-glionated plexuses that control gut innervation the submucous plexus (Meissner s plexus) and the myenteric plexus (Auerbach s plexus). The enteric nervous system and the central nervous system (CNS) are interconnected and interdependent. A number of neurochemicals mediate their function, including serotonin (5-hydroxytryptamine or 5-HT), acetylcholine, substance P, and nitric oxide, among others. 

McQuade, R. Sharp, T. (1997). Functional mapping of dorsal and median raphe 5-hydroxytryptamine pathways in forebrain of the rat using microdialysis. 

Stanford, S. C. (2001). 5-Hydroxytryptamine. In Neurotransmitters, Drugs and Brain Function, ed. R. A. Webster, pp. 187-209. Chichester John Wiley Sons. 

Neurochemical theories for the affective disorders propose that there is a link between dysfunctional monoaminergic synapses within the central nervous system (CNS) and mood problems. The original focus was the neurotransmitter noradrenaline, or NA (note noradrenaline is called norepinephrine, or NE, in American texts). Schildkraut (1965) suggested that depression was associated with an absolute or relative deficiency of NA, while mania was associated with a functional excess of NA. Subsequently, another monoamine neurotransmitter 5-hydroxytryptamine (5-HT), or serotonin, was put forward in a rival indoleamine theory (Chapter 2). However, it was soon recognised that both proposals could be reconciled with the available clinical biochemical and pharmacological evidence (Luchins, 1976 Green and Costain, 1979). 

Nygren, L. G., Fuxe, K., Jonsson, G., and Olson, L. (1974) Functional regeneration of 5-hydroxytryptamine nerve terminals in the rat spinal cord following 5,6-dihydroxytryptamine induced degeneration. Brain Res., 78 377-394. 

Green, A. R., and Grahame-Smith, D. G. (1976) Effects of drugs on the process regulating the functional activity of brain 5-hydroxytryptamine. Nature, 260 487-491. 

Deraet, M., Manivet, P., Janoshazi, A., Callebert, J., Guenther, S., Drouet, L., Launay, J.M. and Maroteaux, L. (2005) The natural mutation encoding a C terminus-truncated 5-hydroxytryptamine 2B receptor is a gain of proliferative functions. Molecular Pharmacology, 67 (4), 983-991. 

Serotonin Binds to 5-hydroxytryptamine (5-HT) receptor to act as excitatory and inhibitory neurotransmitter in its inhibitory function, it can treat anxiety and depression in its excitatory function, it is an antipsychotic. 

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... 

In a series of studies, Markou and her colleagues have sought to identify drugs that ameliorate the changes in brain reward function evoked by nicotine withdrawal (see Kenny and Markon 2001 for review). This review snmmarises the evidence that 5-hydroxytryptamine (5-HT) and, especially, 5-HTia receptors may play an important role in nicotine withdrawal, although the specific nature of the changes evoked... 

Figure 2.18. The major pathway leading to the synthesis and metabolism of 5-hydroxytryptamine (5-HT). Metabolism of tryptophan to tryptamine is a minor pathway which may be of functional importance following administration of a monoamine oxidase (MAO) inhibitor. Tryptamine is a trace amine. L-Aromatic amino acid decarboxylase is also known to decarboxylate dopa and therefore the term "L-aromatic amino acid decarboxylase" refers to both "dopa decarboxylase"...

The role of serotonin (5-hydroxytryptamine, 5-HT) has also been extensively studied in depressed patients. Whereas the overall psycho-physiological effects of noradrenaline in the CNS appear to be linked to drive and motivation, 5-HT is primarily involved in the expression of mood. It is not surprising therefore to find that the serotonergic system is abnormal in depression. This is indicated by a reduction in the main 5-HT metabolite, 5-hydroxy indole acetic acid (5-HIAA), in the cerebrospinal fluid of severely depressed patients and a reduction in 5-HT and 5-HIAA in the limbic regions of the brain of suicide victims. The 5-HT receptor function also appears to be abnormal in depression. This is indicated by an increase in the density of cortical 5-HT2a receptors in the brains of suicide victims and also on the platelet membrane of depressed patients. Platelets may be considered as accessible models of the nerve terminal. 

Mechanism of Action An antihypertensive that depletes stores of catecholamines and 5-hydroxytryptamine in many organs, including the brain and adrenal medulla. Depression of sympathetic nerve function results in a decreased heart rate and a lowering of arterial blood pressure. Depletion of catecholamines and 5-hydrox-ytryptamine from the brain is thought to be the mechanism of the sedative and tran-quilizing properties. Therapeutic Effects Decreases blood pressure and heart rate sedation. 

The neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) is widely distributed in the CNS, subsuming a variety of functions including drive satiety, mood, aggression, anxiety, and compulsive and impulsive behaviors. It may be an important neurotransmitter in psychiatric symptoms commonly associated with PTSD such as aggression, obsessive/intrusive thoughts, alcohol and substance abuse, and suicidal behavior (Friedman, 1990). Suicidal behavior is known to be associated with both childhood maltreatment and low 5-HT functioning (Van der Kolk et ah, 1991 Benkelfat,... 

Cabteta, T.M., and Battaglia, G. (1994) Delayed decreases in brain 5-hydroxytryptamine 2a/2c receptor density and function in male tat ptogeny following ptenatal fluoxetine./ Pharmacol Exp Ther 269 637-645. 

Sizer AR, Long SK, Roberts MHT A modulatory function of 5-hydroxytryptamine in the central nervous system, in Serotonin, CNS Receptors and Brain Function (Advances in the Biosciences, Vol 85). Edited by Bradley PB, Handley SL, Cooper SJ, et al. Oxford, England, Pergamon, 1992, pp 135-146 Skett P Biochemical basis of sex differences in drug metabolism. Pharmacol TTier 38 269-304, 1988... 

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. 

Serotonin A neurotransmitter located in the central nervous system (CNS) that is important in many functions, including mood, arousal, and inhibition of painful stimuli (SYN 5-hydroxytryptamine). 

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