5-Hydroxytryptamine physiologic functions

Serotonin or 5-hydroxytryptamine (5-HT) receptors with 7 subtypes and at least 15 distinct members mediate a diverse array of physiological functions both in the central nervous system and in the periphery (1). Their varied cellular distribution and complex signal transduction in part account... 

The serotonergic system is involved in a large number of physiological functions, resulting from its widespread innervation of the brain. The axons of serotonergic neurons of the midbrain raphe nuclei reach almost every brain structure. Action potentials traveling along these axons release 5-hydroxytryptamine... 

The many investigations which have examined inter alia, the effect on 5-hydroxytryptamine metabolism of convulsant and anticonvulsant drugs, of electroshock and insulin coma, have yielded results which though interesting throw little light on the physiological function of 5-hydroxytrypt-amine . 

In animals, serotonin (5-hydroxytryptamine) is a very important neurotransmitter in the central nervous system and also in the cardiovascular and gastrointestinal systems. The structurally similar hormone melatonin is thought to control the diurnal rhythm of physiological functions. 

Serotonin (53) (5-hydroxytryptamine [5-HT]) is a neurotransmitter that is involved in controlling several physiological functions. Bufotenine (54) (Al,N-dimethyl-5-hydroxytryptamine) is a potent hallucinogen (Scheme 29). As a class, dimethyltryptamines are excellent 5-HTjj ... 

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. 

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. 

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. 

The excretion of amines is unusual in animals. Amines are highly toxic and one method employed by vertebrates to detoxify them is via monoamine oxidase, an enzyme which has been detected in H. diminuta (569). Amines can arise from the decarboxylation of the appropriate amino acid, e.g. glycine and alanine can give rise to methylamine and ethylamine, respectively. Another possible source of amines may be the reduction of azo or nitro compounds (39) and azo- and nitro-reductase activity has been reported from M. expansa (180, 181). Furthermore, the physiologically active amines octopamine, dopamine, adrenalin and serotonin (5-hydroxytryptamine) have been demonstrated in cestodes (283, 296, 435, 681, 682, 758, 859), where they probably function predominantly as neurotransmitters (see Chapter 2). 

Since the discovery of 5-hydroxytryptamine (serotonin, enteramine, thrombocytin) (VII), and the demonstration of its physiological activity and its important function as a neurohormone, the possibility of its occurrence in plants has attracted much attention. It was first shown to be present in Mucuna pruriens DC. (cowhage), and is probably responsible for the intense irritation which results when cowhage comes into contact with the skin (94). This irritation could be a mechanical effect due to the trichomes, but it is more likely to be the result of liberation of... 

Pharmacological evidence was obtained several years ago that indicated that tryptophan is decarboxylated to tryptamine by both animal and bacterial enzymes. More recent studies have failed to detect this reaction, but instead have shown decarboxylation to occur only after oxidation of the indole nucleus to yield 5-hydroxytryptophan. Decarboxylation of 5-hydroxytryptophan produces 5-hydroxytryptamine, serotonin, which has important, though incompletely defined functions in animal physiology. In some animal livers there is an enzyme that decarboxylates cysteic acid to taurine. Glutamic decarboxylase has been found in animal brain, where it is responsible for the formation of 7-aminobutyric acid. This product has been implicated in nervous function as an inhibitor of synaptic transmission. ... 

Noradrenaline, adrenaline, dopamine and serotonin (5-HT, 5-hydroxytryptamine) (Fig. 18.1) are monoamines of fundamental importance in the central nervous system (CNS) because of their function as neurotransmitters. It is therefore not surprising that these compotmds serve as structural templates for medicinal products in the attempt to influence brain signalling mechanisms. Health may often he defined as the absence of illness and, correspondingly, most currently available dmgs have been developed to compensate for a reduced capability of the brain to maintain fimaion-ing. An additional perspective refers to the fact that health and well-being may be viewed as a potential for enhancement beyond what would otherwise be considered as normal physiological and psychological performance. 

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