Disease relevance of serotonin

• Cushing's syndrome due to ectopic ACTH production by a carcinoid tumor not producing serotonin [1].
• Serotonin in essential myoclonus [2].
• Measurements were obtained at base line and during intracoronary infusions of serotonin (0.1, 1, and 10 micrograms per kilogram of body weight per minute, for two minutes) [3].
• Platelets from these three patients had increased levels of IgG and C3, which correlated with the presence of thrombocytopenia; their plasma caused the release of serotonin from normal platelets at concentrations of heparin within the usual therapeutic range [4].
• Serotonin and acute ischemic heart disease [5].
• This study provides evidence that serotonin plays a role in the pathogenesis of steatohepatitis, and therefore might represent a novel target for the prevention and treatment of NASH [6].
• We identified two serotonin receptors that are often overexpressed in human hepatocellular cancer and may serve as a new cytotoxic target [7].

Psychiatry related information on serotonin

• Neurotransmitter-receptor binding sites for apparent muscarinic cholinergic, beta-adrenergic, gamma-aminobutyric acid and serotonin receptors were measured in the caudate nucleus and frontal cerebral cortex from post-mortem brains of 16 patients with Huntington's chorea and 16 controls [8].
• Blood serotonin levels in the attention-deficit disorder [9].
• Presynaptic serotonin receptor-mediated response in mice attenuated by antidepressant drugs and electroconvulsive shock [10].
• "Serotonin depression"--a biochemical subgroup within the affective disorders [11]?
• The finding suggests the existence of a biochemical subgroup of depressive disorder, characterized by a disturbance of serotonin turnover [11].
• To the extent to which predator stress effects model aspects of PTSD, and in the light of relevant human literature, these considerations implicate abnormalities of 5-HT transmission in vulnerability to PTSD per se, and as a potential contributor to enhanced female vulnerability to PTSD [12].

High impact information on serotonin

• The same intersection, when preceded by a third signal, FGF4, which is expressed in the primitive streak, defines an inductive center for hindbrain 5-HT neurons [13].
• In fact, presynaptic sensory neuron axons deprived of their cell bodies are capable of protein synthesis, and this protein synthesis is stimulated 3-fold by exposure to serotonin [14].
• By perfusing serotonin onto the synapses made onto one motor neuron, we found that a single axonal branch can undergo long-term branch-specific facilitation [14].
• We carried out two randomized, double-blind, crossover studies in patients with painful diabetic neuropathy, comparing amitriptyline with the relatively selective blocker of norepinephrine reuptake desipramine in 38 patients, and comparing the selective blocker of serotonin reuptake fluoxetine with placebo in 46 patients [15].
• Effect of intracoronary serotonin on coronary vessels in patients with stable angina and patients with variant angina [16].

Chemical compound and disease context of serotonin

• We evaluated the therapeutic effect of L-5-hydroxytryptophan (L-5HTP), the precursor of serotonin (5-hydroxytryptamine), combined with carbidopa, a peripheral decarboxylase inhibitor, in patients with intention myoclonus and examined the serotonin metabolites in spinal fluid, blood and urine before and during therapy [17].
• Platelets from two patients with essential thrombocythemia failed to aggregate or release serotonin in response to concentrations of epinephrine that aggregated platelets from normal controls [18].
• We postulate that a deficiency of brain serotonin is causally related to intention myoclonus and that the therapeutic effect of L-5HTP and carbidopa may be due to the repletion of serotonin in regions of the brain where serotoninergic neurons have degenerated [17].
• Hyperphagia did not develop despite comparable losses of 5-hydroxytryptamine when the pretreatment was withheld, perhaps because substantial depletions of norepinephrine occurred as well [19].
• We have found that the metabolism of 5-hydroxytryptamine increases in the hippocampus and that the metabolism of dopamine decreases in the striatum and thalamus during slow-wave sleep, and we suggest that these changes are related to this stage of sleep [20].

Biological context of serotonin

• Under limited calcium conditions, where virtually no serotonin release occurs, (Con A)-stimulated phosphorylation is uninhibited [21].
• Serotonin, a major product of platelet activation, has potent vasoactive effects in animal models, but its role in human coronary artery disease remains largely speculative [16].
• The vertebrate retina also exhibits a circadian rhythm of serotonin N-acetytransferase activity (NAT, EC 2.1.1.4), a key enzyme controlling melatonin synthesis, and of photoreceptor disk shedding [22].
• Repeated or prolonged exposure to serotonin or cAMP, which induce long-term changes in synaptic transmission lasting one or more days, induce long-term changes in phosphorylation of the same 17 proteins that are now dependent for their induction on both translation and transcription [23].
• Serotonin caused a slow depolarization of membrane potential of about 5 mV which remained sub-threshold, accompanied by an increase in electrical excitability of the neurone, and an increase in input resistance [24].

Anatomical context of serotonin

• The serotonin level was subnormal in the dorsal raphe nucleus, as was the dopamine level in the nucleus accumbens and, in one of the two cases, in the striatum [25].
• Experimental evidence suggests a central-nervous-system origin of Cushing's disease and a role for serotonin in the regulation of ACTH release [26].
• A study of protein phosphorylation in shape change and Ca++-dependent serotonin release by blood platelets [21].
• In the caudate nucleus of choreic brain, both enzyme activities were markedly lower, with significant decreases in muscarinic cholinergic and serotonin receptor binding, whereas enzyme activities and receptor binding were unchanged in the cerebral cortex [8].
• We repeated the measurements after an infusion of ketanserin, an antagonist of serotonin receptors that is thought to block the effect of serotonin on receptors in the arterial wall but not in the endothelium [3].

Associations of serotonin with other chemical compounds

• Elevated concentrations of norepinephrine were found in the septum, thalamus, colliculi, red nucleus, and dorsal raphe nucleus; of serotonin, in the globus pallidus, subthalamic nucleus, and locus ceruleus; and of 5-hydroxyindoleacetic acid, in the globus pallidus, subthalamic nucleus, and nuclei raphe centralis inferior and obscurus [25].
• Potentiation of central reward by localised perfusion of acetylcholine and 5-hydroxytryptamine [27].
• In addition, some authors have observed that cerebral arteries (such as the vertebrobasilar system of the rabbit) and microvessels may take up serotonin and 5-hydroxytryptophan in various species [28].
• Differential circadian rhythms in pineal and hypothalamic 5-HT induced by artificial photoperiods or melatonin [29].
• Moreover, studies using extracellular single-cell recording techniques indicate that serotonin in small amounts facilitates synaptically or glutamate-induced excitation of mammalian motoneurones in the facial nucleus and spinal cord [24].
• Saturation of lung 5-HT transporters by sertraline prevents the initial trapping of (11)C-DASB [30].
• This result suggests an interaction between the serotonin pathway and the insulin/insulin-like growth factor 1 pathway [31].
• Concurrent chronic administration (14 days) of Org 34850 or Org 34517 enhanced the fluoxetine-induced increase in basal 5-HT [32].
• Methamphetamine-induced 5-HT release remained significantly elevated for more than 2 h after its administration, suggesting that the increased 5-HT could be responsible for the potentiation of methylphenidate-induced locomotor activation [33].
• Block of serotonin transporter (SERT) with citalopram or 5-HT depletion with (+/-)-p-chlorophenylalanine pretreatment partially inhibited the ESP MDMA [34].
• Results of TDC overexpression and TDC RNAi plants suggest that TDC plays a rate-limiting role for serotonin accumulation, but the synthesis of serotonin depends on an absolute amount of tryptophan accumulation by the coordinate induction of the tryptophan biosynthetic genes [35].

Gene context of serotonin

• Here we show that young adult mice with a targeted mutation of the serotonin 5-HT2C receptor gene consume more food despite normal responses to exogenous leptin administration [36].
• The serotonin transporter (5-HTT) mRNA is found in all raphe nuclei and in the hypothalamic dorsomedial nucleus where the 5-HTT mRNA is dramatically reduced following immobilization stress [37].
• Corticosterone, ACTH, and CRF release in vivo is increased in rats by drugs that enhance serotonin function, including serotonin precursors, serotonin uptake inhibitors, serotonin releasers, and direct-acting serotonin agonists [38].
• Serotonin stimulates the release of bio- or immunoassayable CRF from isolated rat hypothalamus in vitro [38].
• Dopa decarboxylase (Ddc) mutations affect synthesis of two of these, dopamine and serotonin [39].
• The effect of 5-HT on PRL release was not affected by blocking the serotonin transporter or the vesicular monoamine transporter [40].
• 5-HT converts the attraction exerted by netrin-1 on posterior TCAs to repulsion [41].
• Genotypes at four individual polymorphisms in SLC6A4 were not associated with platelet 5-HT indices [42].
• The rate-limiting enzyme in the synthesis of peripheral serotonin is tryptophan hydroxylase 1 (TPH1), serotonin can mediate pulmonary arterial smooth muscle cell proliferation via the serotonin transporter (SERT) and serotonin can induce pulmonary vasoconstriction via the 5-HT1B receptor in man [43].

Analytical, diagnostic and therapeutic context of serotonin

• Patients with stable coronary disease do not have the normal vasodilator response to intracoronary serotonin, but rather have progressive constriction, which is particularly intense in small distal and collateral vessels [16].
• Microinjection of the CRE sequence into the nucleus of a sensory neuron selectively blocks the serotonin-induced long-term increase in synaptic strength, without affecting short-term facilitation [44].
• A single application of serotonin, a transmitter that mediates sensitization, to individual sensory and motor cells in dissociated cell cultures leads to enhanced transmitter release from the sensory neurons that is independent of new macromolecular synthesis [44].
• Neurons containing the enzyme aromatic-L-amino-acid decarboxylase (AADC) but lacking either tyrosine hydroxylase or serotonin were found in the spinal cord of neonatal and adult rats by light and electron microscopic immunocytochemistry [45].
• The amebic lysates were shown to contain serotonin by radioimmunoassay, high-performance liquid chromatography, and thin-layer chromatography [46].

References