Disease relevance of NAT

• The alpha-adrenergic inhibition of cAMP accumulation and NAT activity was prevented by pertussis toxin [1].
• Moreover, the existence of bidirectional communication between the pineal gland and the activated immune system was supported by the decreased activity of pineal NAT in chickens with peritonitis compared with control birds [2].
• We previously showed that in Gallus domesticus chicks pretreated with LD12:12, NAT activity was increased by dark exposure (peak dark sensitivity occurred during the expected dark-time) or decreased by light at night (peak light sensitivity occurred early in the night during the time of dark sensitivity) [3].
• Breast cancer, heterocyclic aromatic amines from meat and N-acetyltransferase 2 genotype [4].

High impact information on NAT

• However, I now report that chick pineal glands cultured under a diurnal cycle of illumination exhibit a diurnal cycle in content of cyclic GMP which roughly parallels the cycles in NAT activity [5].
• Levels of serotonin N-acetyltransferase (NAT: acetul CoA:arylamine N-acetyltransferase; EC 2.1.1.5.) activity in the chick pineal gland exhibit a marked diurnal variation in birds kept under a diurnal cycle of ilumination [5].
• In contrast, there was no correlation between variations in pineal content of cyclic AMP and in level of NAT activity [5].
• The mechanism of the 'biological clock' which regulates these variations in level of chick pineal NAT activity is unknown [5].
• I report here that in the dispersed cell culture of chicken pineal gland, N-acetyltransferase activity exhibits a circadian rhythm and responds to environmental lighting in the same manner as in the organ culture [6].

Biological context of NAT

• The supernatant of the homogenate of transfected cells showed a high level of N-acetyltransferase activity with a substrate specificity comparable to that of the liver enzyme [7].
• The complete nucleotide sequence of the cDNA was determined, from which the amino acid sequence of N-acetyltransferase was deduced [7].
• The results revealed seasonal changes in the circadian rhythm of pineal NAT activity occurring in parallel to the natural local geophysical seasons [2].
• During embryonic development, NAT activity was consistently detectable by embryonic day 6 (E6) [8].
• For designation of genotypes at a single NAT* locus, a slash serves to separate the alleles; in phenotype designations, which are not italicized, alleles are separated by a comma [9].

Anatomical context of NAT

• Consistent with the hypothesis that NAT is localized in photoreceptors, the effects of the stimulatory treatments were significantly greater in E6 and E8K cultures than in E8 cultures [10].
• The activity of serotonin N-acetyltransferase (NAT), a key regulatory enzyme in the melatonin biosynthetic pathway, was examined in low-density monolayer cultures of chick embryo retinal cells prepared with three levels of photoreceptor enrichment [10].
• Stimulation of NAT activity by phosphate occurs only in chick pineal and retina, not in chick cerebrum, cerebellum or liver, nor in rat pineal or other tissues tested [11].
• Additionally, bromocriptine and quinpirole displaced the specific binding of [3H]rauwolscine, an alpha-2 adrenergic receptor antagonist, to membranes from chicken pineal gland, with potencies comparable to those observed for inhibition of NAT activity in vitro [12].
• In chicks that have had their superior cervical ganglia removed inactivation of pineal NAT by light is intermediate between that of intact and blind chicks, indicating that ganglionectomy does not completely mimic the effects of blinding [13].

Associations of NAT with chemical compounds

• Two methods were applied to confirm that the cDNA encoded arylamine N-acetyltransferase [7].
• After a partially purified enzyme preparation was absorbed on the column, N-acetyltransferase activity was eluted with 1 M NaCl and 1 M urea [14].
• Midnight illumination induced a dramatic decrease of NAT activity and melatonin release [15].
• It is suggested that prolonged exposure to light or darkness, by altering the level of the retinal dopaminergic neurotransmission, may modify the reactivity of the D4-like dopamine receptors regulating NAT activity of the chick retina [16].
• Systemic administration of clonidine acutely suppressed NAT activity of chick pineal gland, but did not affect the phase of subsequent cycles in constant darkness [17].

Other interactions of NAT

• It is suggested that, although D4-like DA receptors in chick retina are involved in the regulation of NAT activity by the circadian clock, they do not appear to be implicated in the regulation of the clock by light [18].

Analytical, diagnostic and therapeutic context of NAT

• This diurnal cycle in chick pineal NAT activity found in vivo has recently been reproduced in vitro with intact glands incubated in organ culture [5].
• Arylalkylamine (serotonin) N-acetyltransferase assay using high-performance liquid chromatography with fluorescence or electrochemical detection of N-acetyltryptamine [19].

References