Disease relevance of N-acetylserotonin

• The effect of N-acetyl serotonin on ultraviolet-radiation-induced cataracts in rats [1].

High impact information on N-acetylserotonin

• N-acetyl-serotonin reduced lipid peroxidation in testicular microsomes or mitochondria for both C20:4 n6 and C22:5 n6 [2].
• We assayed increasing concentrations (0-10 mM) of N-acetyl-serotonin in testis microsomes and (0-1 mM) of N-acetyl-serotonin in testis mitochondria [2].
• In these experimental conditions, N-acetyl-serotonin was about 18 times more potent in testicular mitochondria in inhibiting the oxidative processes than it was in testicular microsomes [2].
• Control experiments were performed by incubating microsomal and mitochondrial membranes with N-acetyl-serotonin in the absence of lipid peroxidation-inducing drugs [2].
• The 27 amino acid peptide, pituitary adenylate cyclase-activating polypeptide (PACAP-27), and its 38 amino acid analogue, PACAP-38, stimulate serotonin-N-acetyltransferase (NAT) activity and N-acetylserotonin (NAS) and melatonin content of pineal glands from adult rats [3].

Biological context of N-acetylserotonin

• These results suggest that the protective role of N-acetyl-serotonin in preserving the long PUFAs may be related to its ability to reduce lipid peroxidation [2].
• The kinetics of the enzyme reaction for melatonin formation from N-acetyl-serotonin (NAS) and for MeO-E2 were compared [4].
• It is therefore suggested that the up-regulation of beta adrenoceptors noted during the late afternoon and early evening hours corresponds to the increased synthesis of 5-HT and the subsequent conversion to NAS [5].
• Melatonin is metabolised by hydroxylation to form 6-hydroxy-melatonin and by demethylation to form N-acetyl-serotonin, which are excreted as sulphate and glucuronide conjugates [6].
• The final step of melatonin (MLT) synthesis is methylation of N-acetyl-serotonin, with S-adenosylmethionine as a methyl donor provided by a metabolic pathway involving sulfur-containing amino acids (homocysteine and methionine) [7].

Anatomical context of N-acetylserotonin

• Both long chain PUFAs were protected when N-acetyl-serotonin was incorporated either into microsomes or mitochondria [2].
• Noradrenergic stimulation of cultured pineals led to a predictable increase in N-acetyl-serotonin and melatonin production, suggesting that the method was useful for biochemical and pharmacological studies on the pineal gland [8].
• IC 50 values calculated from the inhibition curve of N-acetyl-serotonin on the chemiluminescence rates were higher in microsomes (4.50 mM) than in mitochondria (0.25 mM) [2].
• Pineal glands were divided sagittally and a single half was used to measure 5-HT, NAS, and melatonin concentrations, while the remaining half from the same gland was employed to assess changes in the density of beta adrenoceptors on partially purified membranes [5].
• Hen choroid and iris-ciliary body O-methylated NAS and HTOL, whereas rabbit choroid and, to a much lesser extent, hypothalamus and cerebral cortex all O-methylated only NAS [9].

Associations of N-acetylserotonin with other chemical compounds

• Human pineal glands obtained from 77 post-mortem sources from various age groups and times of death were used to examine the 24-hour cycle of serotonin (5-HT), melatonin, N-acetylserotonin (NAS), and beta adrenoceptor density [5].
• In an in vitro system, the presence of neopterin or tetrahydrobiopterin or the pterin synthesis inhibitor, N-acetyl serotonin, did not modulate cytotoxic effects of lymphokine-activated killer cells [10].
• The structural similarity of the tyrosinamide end of scotophobin A to NAS and several other HIOMT inhibitors, including two antischizophrenic drugs, is consistent with these observations [11].
• For subcuticular injection of amines (0.15 ml, 10(-2) mol l(-1)), the interval of the refractory stage was shortened by octopamine, serotonin, 5-hydoxytryptophan and N-acetyl-serotonin but was unchanged by tryptophan, melatonin or 5-hydroxyindol-3-acetic acid [12].
• NAS and methylene blue, an inhibitor of monoamine oxidase A, attenuated light-induced disruption of NAS but not melatonin rhythms [13].

Gene context of N-acetylserotonin

• The SR activity of the recombinant protein was inhibited by two indoleamines, N-acetyl serotonin and melatonin [14].
• In conclusion, it may be inferred that CYP2C19 substrate slows the metabolism of exogenous melatonin and increases its bioavailability, as shown by the augmented excretion of aMT6S, probably by inhibiting the conversion of melatonin to NAS via CYP2C19 isozyme [15].
• This effect, in turn, was reversed by the inhibitor of sepiapterin reductase, N-acetyl-serotonin [16].
• The production of PLP from pyridoxal (PL) by pyridoxal kinase (PLK) was inhibited by the addition of dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT), but not by that of epinephrine and N-acetyl-serotonin [17].
• N-acetyl-serotonin has recently been identified as a potent antioxidant against free radical stress [18].

Analytical, diagnostic and therapeutic context of N-acetylserotonin

• Organ cultures of pineal glands from rats treated chronically with alpha-methyldopa showed enhanced conversion of radio-active serotonin to melatonin (aMT) as well as its precursor, N-acetyl-serotonin (aHT) [19].

References