Psychiatry related information on Aanat

• Intraperitoneal cocaine treatment (10 and 20 mg/kg) dose-dependently increased locomotor activity of both normal (C3H/HeJ) and AANAT mutant (C57BL/6J) mice; this effect was similar during the day and at night [1].

High impact information on Aanat

• The enzyme serotonin N-acetyltransferase (NAT) catalyzes the rate limiting step in melatonin synthesis [2].
• None of the antibodies cross-reacted with arylamine N-acetyltransferase from the livers of cow, rabbit, and rat, nor with arylalkylamine N-acetyltransferase from the chicken pineal gland, indicating a high specificity of the antibodies [3].
• We recently demonstrated that stimulation of beta-adrenergic receptors only increases nighttime arylalkylamine N-acetyltransferase (Aa-Nat, the rate-limiting enzyme in melatonin synthesis) mRNA levels in mouse pineal gland in vitro, which suggests that pineal clocks may gate Aa-Nat gene expression [4].
• Role of calcium in the gating of isoproterenol-induced arylalkylamine N-acetyltransferase gene expression in the mouse pineal gland [4].
• Serotonin N-acetyltransferase (AANAT; EC 2.3.1.87) metabolizes serotonin into N-acetylserotonin (NAS) [5].

Biological context of Aanat

• The locus controlling pineal serotonin N-acetyltransferase activity (Nat-2) is located on mouse chromosome 11 [6].
• This finding suggests that the c-FOS/c-JUN dimer is required for transcriptional activation of the Aanat gene [7].
• The primary structure of serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AA-NAT: the rate-limiting enzyme in melatonin synthesis) in the mouse retina was deduced from the cDNA nucleotide sequence [8].
• Pineal circadian clocks gate arylalkylamine N-acetyltransferase gene expression in the mouse pineal gland [9].
• This rhythm involves the transcriptional regulation of the AANAT by two norepinephrine (NE)-inducible transcription factors, e.g. the activator pCREB (phosphorylated Ca2+/cAMP-response element binding protein) and the inhibitor ICER (inducible cAMP early repressor) [10].

Anatomical context of Aanat

• The inhibitory transcription factor ICER is present in the pineal gland but with highest values when AANAT may be activated, suggesting the blockade takes place upstream of Aanat expression [7].
• N-acetyltransferase activity toward the aromatic amine carcinogen 4-aminobiphenyl and O-acetyltransferase activity toward its proximate metabolite N-hydroxy-4-aminobiphenyl were both present in tissue cytosols of WT mice but were undetectable in Nat2 KO mice [11].
• 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 [5].

Associations of Aanat with chemical compounds

• Melatonin is synthesized from serotonin by the enzymes serotonin N-acetyltransferase (SNAT) and hydroxyindole-O-methyl-transferase (HIOMT) [6].
• The rhythmicity of melatonin synthesis is regulated by the rhythmic activity of SNAT [12].
• Interestingly, injection of the protein synthesis inhibitor cycloheximide before, but not after, the c-FOS/c-JUN peak markedly reduces Aanat mRNA levels [7].
• Circadian differences in behavioral sensitization to cocaine: putative role of arylalkylamine N-acetyltransferase [1].
• AANAT expression and synthesis of N-acetylserotonin/melatonin could play a role in addictive properties of cocaine [1].

Other interactions of Aanat

• The molecular linkage analysis demonstrated that the gene encoding SNAT maps 1.5 cM distal to D11Mit11 [12].
• We observed that mice with both outer-retinal degeneration and a deficiency in melanopsin exhibited complete loss of photoentrainment of the circadian oscillator, pupillary light responses, photic suppression of arylalkylamine-N-acetyltransferase transcript, and acute suppression of locomotor activity by light [13].

Analytical, diagnostic and therapeutic context of Aanat

• In the present study, the gene encoding SNAT was localized, using a rat cDNA fragment, on rat and mouse chromosomes by direct R-banding fluorescence in situ hybridization (FISH) [12].
• Molecular cloning of serotonin N-acetyltransferase gene from the mouse and its daily expression in the retina [8].
• These findings suggest that the expression mechanism of AA-NAT transcripts in the mouse retina may be different from those in other mammals, where a single transcript of AA-NAT is normally observed in Northern blots [8].
• Nat1- and Nat2-specific mRNA, determined by quantitative real-time polymerase chain reaction, was detected in all tissues examined and did not differ significantly (p > 0.05) between Nat2 KO and WT mice [11].

References