Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA, USA.
Department of Biology, University of Washington, Seattle, WA, USA.
J Pineal Res. 2020 Mar;68(2):e12622. doi: 10.1111/jpi.12622. Epub 2019 Dec 30.
At night, the pineal gland produces the indoleamines, melatonin, N-acetylserotonin (NAS), and N-acetyltryptamine (NAT). Melatonin is accepted as a hormone of night. Could NAS and NAT serve that role too?
Concentration-response measurements with overexpressed human melatonin receptors MT and MT ; mass spectrometry analysis of norepinephrine-stimulated secretions from isolated rat pineal glands; analysis of 24-hour periodic samples of rat blood.
We show that NAT and NAS do activate melatonin receptors MT and MT , although with lower potency than melatonin, and that in vitro, melatonin and NAS are secreted from stimulated, isolated pineal glands in roughly equimolar amounts, but secretion of NAT was much less. All three were found at roughly equal concentrations in blood during the night. However, during the day, serum melatonin fell to very low values creating a high-amplitude circadian rhythm that was absent after pinealectomy, whereas NAS and NAT showed only small or no circadian variation.
Blood levels of NAS and NAT were insufficient to activate peripheral melatonin receptors, and they were invariant, so they could not serve as circulating hormones of night. However, they could instead act in paracrine circadian fashion near the pineal gland or via other higher-affinity receptors.
夜间，松果腺会产生吲哚胺、褪黑素、N-乙酰血清素（NAS）和 N-乙酰色胺（NAT）。褪黑素被认为是夜间的激素。那么 NAS 和 NAT 是否也可以起到这种作用呢？
使用过表达的人褪黑素受体 MT 和 MT 进行浓度-反应测量；用质谱分析法分析分离的大鼠松果腺中去甲肾上腺素刺激后的分泌物；分析大鼠血液 24 小时周期样本。
我们发现，NAT 和 NAS 确实可以激活褪黑素受体 MT 和 MT ，尽管其效力低于褪黑素，而且在体外，从受刺激的分离的松果腺中以大致等摩尔量分泌褪黑素和 NAS，但 NAT 的分泌量要少得多。这三种物质在夜间的血液中浓度大致相等。然而，在白天，血清褪黑素降至非常低的水平，产生了一个高振幅的昼夜节律，这种节律在松果腺切除后消失，而 NAS 和 NAT 只显示出较小或没有昼夜变化。
血液中 NAS 和 NAT 的水平不足以激活外周褪黑素受体，而且它们没有变化，因此不能作为夜间的循环激素。然而，它们可以通过旁分泌的昼夜节律方式在松果腺附近发挥作用，或者通过其他高亲和力受体发挥作用。
