Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: CAS:50-67-9 (5-HT)
31,727 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because NO is not very reactive in an oxygen-free buffer, a significant part of serotonin (5-HT) is transformed by NO in nondeaerated phosphate buffer, at pH 7.4, into (4-serotonyl)-4-serotonin, 4-nitrososerotonin, and 4-nitroserotonin. Dimerization and above all nitrosation occur through the HNO2 reaction in the pH 4-6 range, possibly via radical mechanism involving N2O3. 5-HT is readily a substrate for nitrosation by HNO2 or N2O3, whereas tyrosine was described as not very reactive under the same conditions. Peroxynitrite converts 5-HT to the (4-serotonyl)-4-serotonin and to the 4-nitro derivative. In order to evaluate whether such structural modifications could modulate the biological properties of 5-HT, arterial pressure was measured after i.v. bolus injection of these derivatives to anesthetized rats. Injections of the 4-nitroso- and 4-nitro-5-HT resulted in first a brief hypotensive response and did not give the subsequent hypertensive and hypotensive phases observed with 5-HT. Finally, when tested on some cloned rat 5-HT receptors stably transfected into LMTK- cells, both 4-nitroso and 4-nitro derivatives behaved as agonists and antagonists toward 5-HT1B and 5-HT2B receptors, respectively.
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PMID:Oxidation, nitrosation, and nitration of serotonin by nitric oxide-derived nitrogen oxides: biological implications in the rat vascular system. 1063 29

The effects of trazodone on the cyclic GMP elevation elicited by N-methyl-D-aspartate in rat cerebellar slices were analyzed. Trazodone inhibited in a concentration-dependent manner (EC50 = 0.82 nM) the cyclic GMP response evoked by 0.1 microM N-methyl-D-aspartate. The inhibition was near complete at 10 nM trazodone. The effect of 10 nM trazodone was unaffected by 0.3 microM spiperone or rauwolscine, antagonists with selectivity for the 5-HT(serotonin)2A or the 5-HT2B subtype, respectively, but it was totally prevented by 0.01 microM mesulergine, a 5-HT2A/5-HT2B/5-HT2C receptor antagonist. Trazodone was potently counteracted (IC50 = 2.7 nM) by the selective 5-HT2B/5-HT2C receptor antagonist N-(1-methyl-5-indolyl)-N-(3-pyridil) urea HCl and, less potently (IC50 = 95 nM), by ketanserin, a 5-HT2A/5-HT2C receptor blocker. It is concluded that trazodone behaves as a potent full agonist at the 5-HT2C receptor mediating inhibition of the cerebellar N-methyl-D-aspartate/nitric oxide/cyclic GMP system.
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PMID:Trazodone is a potent agonist at 5-HT2C receptors mediating inhibition of the N-methyl-D-aspartate/nitric oxide/cyclic GMP pathway in rat cerebellum. 961 98

The enteric nervous system is derived from the vagal, rostral-truncal, and sacral levels of the neural crest. Because the crest-derived population that colonizes the bowel contains multipotent cells, terminal differentiation occurs in the gut and is influenced by both the enteric microenvironment and the responsivity of multiple lineages of precursors. Enteric growth factor-receptor combinations, which promote the development of enteric neurons and/or glia in most of the gastrointestinal (GI) tract, include glial cell line-derived neurotrophic factor-GFRalpha-1-Ret, NT-3-TrkC, a still-to-be-identified neuropoietic cytokine-ciliary neurotrophic factor receptor-alpha, serotonin (5-HT)-5-HT2B, and LBP110, a 110-kDa laminin-1 binding protein. A qualitatively different effect is shown by the peptide-receptor combination ET-3-ETB, which inhibits neuronal differentiation and appears to prevent the premature differentiation of enteric neurons before colonization of the GI tract has been completed (resulting in aganglionosis of the terminal colon).
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PMID:V. Genes, lineages, and tissue interactions in the development of the enteric nervous system. 981 12

The effects of a serotonin (5-HT) releasing drug, p-chloroamphetamine, on plasma glucose levels were investigated in rats. p-Chloroamphetamine elicited a significant hyperglycemia. The hyperglycemic effects of p-chloroamphetamine were completely prevented by the 5-HT synthesis inhibitor, p-chlorophenylalanine. Prior adrenodemedullation abolished the hyperglycemia elicited by p-chloroamphetamine. p-Chloroamphetamine-induced hyperglycemia was prevented by methysergide, which blocks the 5-HT1 and 5-HT2 receptor, the 5-HT1A/1B/2C receptor antagonist, (-)-propranolol, the selective 5-HT1A receptor antagonist, 4-(2'-methoxyphenyl-1-[2'-n-2"pyridinyl)-p-iodobenzamido]-ethyl-pi perazine (p-MPPI), the 5-HT2A/2B/2C receptor antagonists, ritanserin and 4-isopropyl-7-methyl-9-(2-hydroxy-1-methyl-propoxycarbonyl)-4,6A,7 ,8,9,10,10A-octahydro-indolo[4,3-FG]quinolone maleate(LY 53857). However, the 5-HT3 and 5-HT4 receptor antagonist, tropisetron, the 5-HT4 receptor antagonist, 2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino) ethyl ester (SDZ 205-557), and the 5-HT2A receptor antagonist, ketanserin, did not affect the p-chloroamphetamine-induced hyperglycemia. These results suggest that p-chloroamphetamine-induced hyperglycemia is elicited by an enhanced 5-HT release and facilitated adrenaline release. Moreover, our results indicate that p-chloroamphetamine-induced hyperglycemia is mediated by 5-HT1A and 5-HT2B/2C receptors.
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PMID:p-Chloroamphetamine, a serotonin-releasing drug, elicited in rats a hyperglycemia mediated by the 5-HT1A and 5-HT2B/2C receptors. 983 90

[3H]5-HT revealed the presence of serotonin receptors in cultured rat sensory neurons. [3H]5-CT binding was inhibited by cyanopindolol with an IC50 of 0.87 +/- 0.30 nM, suggesting the expression of the 5-HT1B receptor in these neurons. The presence of 5-HT1B receptors was confirmed by the displacement of [125I]Iodocyanopindolol binding by cyanopindolol with an IC50 of 2.43 +/- 0.81 nM. 5-HT1B receptors are the predominant type of serotonin receptors labeled by [3H]5-HT in cultured DRG neurons, representing approximately 60% of the specific [3H]5-HT binding sites. In addition, 5-HT1D and 5-HT2A receptor binding was also found in these neurons. RT-PCR analysis of RNA isolated from embryonic sensory neurons in culture confirmed the expression of 5-HT1B, 5-HT1D and 5-HT2A receptor mRNA. It also demonstrated the presence of 5-HT1F, 5-HT2C, 5-HT3, 5-HT4, 5-HT5A and 5-HT5B receptor mRNA and the absence of 5-HT1A, 5-HT1E, 5-HT2B, 5-HT6 and 5-HT7 mRNA. The identification of multiple subtypes of serotonin receptors expressed in cultured embryonic sensory neurons suggests that DRG neuronal cultures may be an excellent model to examine the direct effects of serotonin on the activity of these sensory neurons.
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PMID:Multiple subtypes of serotonin receptors are expressed in rat sensory neurons in culture. 986 1

Anxiety disorders are heterogeneous and existing animal models do not discriminate specific types of anxiety. The elevated T-maze is being developed to fulfill this purpose. The apparatus consists of three elevated arms, one enclosed and two open. Inhibitory avoidance--representing learned fear--is measured by recording the time taken to leave the enclosed arm in three consecutive trials. Unconditioned fear is evaluated by recording the time to escape from the open arm. Restraining the animals at the end of the enclosed arm for 30 s did not change the first (baseline) withdrawal latency, indicating that rats are not escaping from the experimenter's hand. In addition, rats trained in a T-maze with the three arms enclosed did not show the usual increase in withdrawal latency over the three consecutive trials. These results indicate that open arm experience, not handling, motivates inhibitory avoidance learning. The same experiment also showed that the latency to leave the open arm did not undergo habituation over five consecutive trials, thereby providing evidence of an aversive motivation for this response. The anxiolytic agents diazepam (benzodiazepine), buspirone and ipsapirone (5-HT1A agonists) as well as ritanserin (5-HT2 antagonist) selectively impaired inhibitory avoidance while leaving one-way escape unchanged. Similar results were obtained with three putative anxiolytics: the 5-HT2B/2C antagonists SB 200646A and SER 082, and the 5-HT2A antagonist SR 46349B. However, RP 62203, another 5-HT2A antagonist, was ineffective on both tasks. In contrast to the above anxiolytics, the anxiogenic agents yohimbine, TFPP and mCPP facilitated inhibitory avoidance. Escape was not affected by yohimbine, but was moderately attenuated by the two 5-HT2C/2B agonists. The 5-HT releaser and uptake inhibitor D-fenfluramine tended to enhance inhibitory avoidance, while impairing one-way escape in a dose-dependent way. The antidepressant clomipramine also had an anxiogenic-like effect on inhibitory avoidance, but did not affect escape from the open arm. Conversely, the phenethylamine hallucinogen ALEPH 2 did not affect inhibitory avoidance while impairing escape. Nevertheless, the similar compound and 5-HT2A agonist DOI was devoid of any effect. Also ineffective were the psychomotor stimulants D,L-amphetamine and caffeine, the reversible monoaminoxidase-A inhibitor moclobemide and the neuroleptic haloperidol. Finally, micro-injection into the dorsal raphe nucleus of two drugs that stimulate 5-HT neurons, the excitatory amino acid kainic acid and the benzodiazepine inverse agonist FG 7142, facilitated inhibitory avoidance. Kainate also significantly impaired escape. In contrast, intra-raphe 8-OH-DPAT, which inhibits 5-HT neurons, selectively impaired inhibitory avoidance in a manner similar to systemically administered anxiolytics. These behavioral and pharmacological results support the view that inhibitory avoidance in the elevated T-maze may be related to generalized anxiety disorder, while one-way escape may be associated with panic disorder.
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PMID:The elevated T-maze as an experimental model of anxiety. 988 16

The aim of this study is to clarify the serotonin (5-HT) receptor subtypes responsible for 5-HT-induced nitric oxide (NO) production in cultured human coronary artery endothelial cells (HCAECs). Reverse transcription-polymerase chain reactions revealed that HCAECs possessed only 5-HT1B and 5-HT2B receptor mRNAs. 5-HT (0.001-10 mumol/L) induced nitrite production from HCAEC. A selective 5-HT1B/1D agonist sumatriptan (0.01-10 mumol/L) caused nitrite production. A selective 5-HT2 agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI, 0.01-10 mumol/L) also mimicked the effect of 5-HT. The 5-HT-induced nitrite production was completely inhibited by the nonselective 5-HT1/2 antagonist methiothepin (0.1 mumol/L), but not by the 5-HT2A/2C antagonist ketanserin (0.1 mumol/L). Each of these agonists evoked the elevation of intracellular Ca2+ concentration in HCAECs. These findings suggest that 5-HT-induced NO production is mediated by both of 5-HT1B and 5-HT2B receptor activation in HCAECs. Thus, the 5-HT-evoked endothelium-dependent relaxation of human coronary arteries in vivo might be evoked by net effects of the activation of these receptor subtypes.
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PMID:Nitric oxide is produced via 5-HT1B and 5-HT2B receptor activation in human coronary artery endothelial cells. 1003 60

5-Hydroxytryptamine (5-HT) has been implicated in pulmonary hypertension, hypoxic pulmonary vasoconstriction, and the pulmonary side-effects of some drugs. 5-HT contracts bovine, ovine, canine, caprine, feline, rabbit, guinea-pig and rat isolated pulmonary arteries mainly by activation of 5-HT2A receptors but relaxes porcine pulmonary artery through activation of endothelial 5-HT2B receptors. Pharmacological responses of the pulmonary veins to 5-HT have been less studied and comprise both contraction (bovine, canine, feline, equine, rabbit) and relaxation (ovine, caprine). Functional and radioligand binding studies in human isolated intrapulmonary arteries and veins have demonstrated a mixed population of 5-HT1B/1D and 5-HT2A receptors mediating vasoconstriction but no evidence of involvement of 5-HT1A, 5-HT3 and 5-HT4 receptors. Remarkable differences exist in the in vitro pulmonary vasoreactivity to 5-HT and related drugs in humans compared with other mammals. Therefore, the use of human tissues is to be preferred to study pathophysiological responses of pulmonary circulation with clinical relevance.
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PMID:Species differences in the responses of pulmonary vascular preparations to 5-hydroxytryptamine. 1021 31

The 5-HT2 receptor agonist, DOI, dose-dependently (0.16-10.0 mg/kg, s.c.) increased dialysate levels of dopamine (DA) and noradrenaline (NA), but not 5-HT, in the frontal cortex (FCX) of freely-moving rats. This action was abolished by the selective 5-HT2A antagonist, MDL100,907 (0.04), which did not, itself, modify levels of DA and NA. In contrast, the selective 5-HT2B/2C antagonist, SB206,553 (0.63), increased levels of DA and NA additively with DOI. Thus, in contrast to a tonic, inhibitory influence of 5-HT2C receptors (see Millan, M.J., Dekeyne, A., Gobert, A., 1998. Serotonin (5-HT)2C receptors tonically inhibit dopamine (DA) and noradrenaline (NAD), but not 5-HT, release in the FCX in vivo. Neuropharmacology 37, 953-955), 5-HT2A receptors exert a phasic, facilitatory influence upon FCX levels of DA and NA.
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PMID:Serotonin (5-HT)2A receptor activation enhances dialysate levels of dopamine and noradrenaline, but not 5-HT, in the frontal cortex of freely-moving rats. 1021 74

The atypical antipsychotic olanzapine has relatively high affinity for a number of neuronal receptors in radioreceptor binding assays. The ability of olanzapine to activate or antagonize a number of neuronal receptors was investigated in vitro, in cell lines transfected selectively with receptor subtypes and in receptor-selective isolated tissue studies. Olanzapine had no agonist activity at any of the receptors examined. However, olanzapine was a potent antagonist of 5-HT-stimulated increases in IP3 in cell lines transfected with 5-HT2A or 5-HT2B receptors with IC50 values of 30-40 nM. Olanzapine weakly blocked 5-HT-induced formation of IP3 in cell lines transfected with 5-HT2c receptors, but in this cell line potently inhibited 5-HT-stimulated [35S]GTP gamma S binding with a Ki value of 15 nM. Olanzapine blocked dopamine-stimulated adenylyl cyclase in rat retina with modest potency (Ki = 69 nM), consistent with its relatively low affinity for dopamine D1 receptors. Olanzapine blocked agonist-induced activities at the muscarinic receptor subtypes M1, M2, M3, and M5 with Ki values of 70, 622, 126, and 82 nM, respectively. In studies using cell lines transfected with muscarinic M4 receptors, olanzapine and the atypical antipsychotic clozapine did not have agonist activities as determined with cAMP inhibition and stimulation assays, arachidonic acid release and [35S]GTP gamma S binding assays. However, olanzapine antagonized agonist-induced effects in muscarinic M4 cells with a Ki value of 350 nM. In isolated tissue studies, olanzapine potently blocked agonist-induced effects at alpha 1-adrenergic and histamine H1 receptors (KB = 9 and 19 nM, respectively). Thus, olanzapine was an antagonist at all receptors investigated and was a particularly potent antagonist at 5-HT2A, 5-HT2B, 5-HT2C, alpha 1-adrenergic and histamine H1 receptors. Olanzapine was a weaker antagonist at muscarinic and dopamine D1 receptors.
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PMID:Antagonism by olanzapine of dopamine D1, serotonin2, muscarinic, histamine H1 and alpha 1-adrenergic receptors in vitro. 1022 13


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