Disease relevance of N-acetylserotonin

• We also documented both the in vitro transformation of serotonin to N-acetylserotonin using liquid chromatography/mass spectrometry and the generation/storage of N-acetylserotonin in cultured melanoma cells [1].
• N-Acetylserotonin prevents the hypotension induced by bacterial lipopolysaccharides in the rat [2].
• In rainbow trout forced to swim continuously at sustained speeds for six weeks, selected doses of melatonin or N-acetylserotonin (1.25 and 5.0 mg/kg body weight) injections caused no change in haematocrit [3].
• 1. The effects of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and N-acetyl-5-hydroxytryptamine on oocytes of Blaberus craniifer, in which vitellogenesis was prevented by imaginal molt decapitation, were investigated [4].

High impact information on N-acetylserotonin

• Inhibition of BH4 biosynthesis in rapidly dividing MEL cells with N-acetylserotonin, a potent inhibitor of sepiapterin reductase, the terminal enzyme in the BH4 biosynthetic pathway, results in inhibition of DNA synthesis and mitogenesis without induction of hemoglobin synthesis [5].
• Retinal ganglion cells are autonomous circadian oscillators synthesizing N-acetylserotonin during the day [6].
• Biotransformation of [3H]serotonin by cultured hamster skin to 3H-metabolites corresponding to N-acetylserotonin (NAS), melatonin, and 5-methoxytryptamine (5-MT) was demonstrated [7].
• AA-NAT leads to formation of N-acetylserotonin from serotonin, and in the pineal gland, to melatonin synthesis [8].
• Vitamin E consumption induced by oxidative stress in red blood cells is enhanced by melatonin and reduced by N-acetylserotonin [9].

Biological context of N-acetylserotonin

• None of the inhibitors that were tested, including N-chloroacetyl-dopamine and N-acetylserotonin, which are specific for sepiapterin reductase, can block MEL cells in G1-phase or induce the cells to commit to terminal differentiation [10].
• The ontogeny of diurnal rhythm patterns in the pineal and serum levels of melatonin, serotonin, and N-acetylserotonin was studied in Syrian hamsters (Mesocricetus auratus) from birth to adulthood [11].
• Thus, 10 mm melatonin and 2 mm N-acetylserotonin produced a reduction of 51 +/- 6 and 100% in the total chemiluminescene (lipid peroxidation), respectively [12].
• Competition binding assays in SK-Mel 28 cells demonstrated the presence of binding sites to 2-[125 I]-iodomelatonin, which was displaced by the unlabelled hormone, by both antagonists, and by N-acetylserotonin [13].
• Studies on the kinetics of melatonin and N-acetylserotonin in the rat at mid-light and mid-dark [14].

Anatomical context of N-acetylserotonin

• Mesenteric arteries from both rat groups were unresponsive to the serotonin metabolite N-acetylserotonin [15].
• We compared the in vitro protective effect of melatonin and N-acetylserotonin on the ascorbate-Fe2+ induced lipid peroxidation of PUFAs located in ROS membranes [12].
• It was proposed that NAS could be a mediator of the antidepressant action of drugs, and it was shown that chronic but not acute treatment of rats with the antidepressant fluoxetine increases the content of AANAT mRNA in the rat hippocampus [16].
• When the cultured chromaffin cells were treated for 72 h with N-acetylserotonin, an inhibitor of sepiapterin reductase, tetrahydrobiopterin content and the rate of tyrosine hydroxylation were decreased [17].
• N-acetylserotonin (NAS) and 5 methoxytryptamine (5MTT) were generally without effect on cell proliferation, with the exception of an inhibition of melanocyte proliferation at the higher 5MTT concentration of 10(-10) M [18].

Associations of N-acetylserotonin with other chemical compounds

• The concentrations of each indole required to reduce DNA damage by 50%, i.e. the IC50 values, were 0.48, 0.51, 0.88, 1.00 and 3.08 microM for pinoline, melatonin, N-acetylserotonin, 6-hydroxymelatonin and indole-3-propionic acid, respectively [19].
• A systematic study of cross-reactions with seven compounds (indole, aromatic and imidazole derivatives) showed that the antibody had a high specificity for melatonin, low reactivity with 6-hydroxymelatonin and N-acetyl-5-hydroxytryptamine, and no detectable reactivity with tryptamine, l-tryptophan, 5-methoxytryptamine and N-acetyl-l-tryptophan [20].
• Alloxan-induced diabetes and the pineal gland: differential effects on the levels of pineal N-acetylserotonin, pineal melatonin, and serum melatonin [21].
• The order of potency--melatonin much less than N-acetyl-5-hydroxytryptamine less than 5-methoxytryptamine much less than 5-hydroxytryptamine = 3,4-dihydroxyphenylethylamine = noradrenaline--shows high specificity of the binding sites for melatonin [22].
• Relative potencies of melatonin agonists to induce phosphoinositide hydrolysis were as follows: 2-iodomelatonin > 6-chloromelatonin > N-acetylserotonin > melatonin > > serotonin (5-HT) [23].

Gene context of N-acetylserotonin

• In conclusion, these results indicate that human UGT1A6 plays a predominant role in the glucuronidation of 5-hydroxytryptophol and N-acetylserotonin, whereas 6-hydroxymelatonin is not a substrate for this enzyme [24].
• N-acetylserotonin was glucuronidated most extensively by UGT1A6, although UGT1A9 and UGT1A10 showed moderate catalysis [24].
• We have investigated the effects of an inhibitor of BH4 synthesis, N-acetyl-5-hydroxytryptamine (N-acetylserotonin, NAS), on the expression of iNOS in cultured macrophages and smooth muscle cells in vitro, and on the hypotensive response to bacterial lipopolysaccharide (LPS) in the anaesthetized rat in vivo [25].
• AANAT expression and synthesis of N-acetylserotonin/melatonin could play a role in addictive properties of cocaine [26].
• METHODS: The formation kinetics of 6-hydroxymelatonin and N-acetylserotonin were determined using human liver microsomes and cDNA yeast-expressed human enzymes (CYP1A2, 2C9 and 2C19) over the substrate concentration range 1-1000 microM [27].

Analytical, diagnostic and therapeutic context of N-acetylserotonin

• Acute immobilization stress suppressed the dark-induced elevations of pineal NAT activity and NAS levels 10 h after the stress session without altering pineal beta-adrenergic receptor binding [28].
• After the intravenous injection of melatonin (10 micrograms), N-acetylserotonin (10 micrograms), or 3H-melatonin (76 ng), blood samples were collected at 1, 3, 5, 10, 20, 30, 45, 60, 75, 90, and 120 min [14].
• N-acetylserotonin and melatonin released into the medium was extracted and then quantified by radioimmunoassay [29].
• Identities of melatonin and N-acetylserotonin were confirmed by thin-layer chromatography [30].
• Using two immunocytochemical procedures (i.e., immunofluorescence and the unlabeled peroxidase-antiperoxidase method), the localization of a serotonin(HT)-like and of a N-acetylserotonin (aHT)-like immunoreactivity in the pineal organ of the pike was studied during winter [31].

References