Serotonin modulates melatonin synthesis as an autocrine neurotransmitter in the pineal gland

2021 ◽  
Vol 118 (43) ◽  
pp. e2113852118
Author(s):  
Bo Hyun Lee ◽  
Bertil Hille ◽  
Duk-Su Koh

The pineal gland secretes melatonin principally at night. Regulated by norepinephrine released from sympathetic nerve terminals, adrenergic receptors on pinealocytes activate aralkylamine N-acetyltransferase that converts 5-hydroxytryptamine (5-HT, serotonin) to N-acetylserotonin, the precursor of melatonin. Previous studies from our group and others reveal significant constitutive secretion of 5-HT from pinealocytes. Here, using mass spectrometry, we demonstrated that the 5-HT is secreted primarily via a decynium-22–sensitive equilibrative plasma membrane monoamine transporter instead of by typical exocytotic quantal secretion. Activation of the endogenous 5-HT receptors on pinealocytes evoked an intracellular Ca2+ rise that was blocked by RS-102221, an antagonist of 5-HT2C receptors. Applied 5-HT did not evoke melatonin secretion by itself, but it did potentiate melatonin secretion evoked by submaximal norepinephrine. In addition, RS-102221 reduced the norepinephrine-induced melatonin secretion in strips of pineal gland, even when no exogenous 5-HT was added, suggesting that the 5-HT that is constitutively released from pinealocytes accumulates enough in the tissue to act as an autocrine feedback signal sensitizing melatonin release.

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Morten Møller ◽  
Pansiri Phansuwan-Pujito ◽  
Corin Badiu

Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with largeboutons en passageand primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.


2021 ◽  
Vol 22 (13) ◽  
pp. 7232
Author(s):  
Gloria Lazzeri ◽  
Carla L. Busceti ◽  
Francesca Biagioni ◽  
Cinzia Fabrizi ◽  
Gabriele Morucci ◽  
...  

Norepinephrine (NE) neurons and extracellular NE exert some protective effects against a variety of insults, including methamphetamine (Meth)-induced cell damage. The intimate mechanism of protection remains difficult to be analyzed in vivo. In fact, this may occur directly on target neurons or as the indirect consequence of NE-induced alterations in the activity of trans-synaptic loops. Therefore, to elude neuronal networks, which may contribute to these effects in vivo, the present study investigates whether NE still protects when directly applied to Meth-treated PC12 cells. Meth was selected based on its detrimental effects along various specific brain areas. The study shows that NE directly protects in vitro against Meth-induced cell damage. The present study indicates that such an effect fully depends on the activation of plasma membrane β2-adrenergic receptors (ARs). Evidence indicates that β2-ARs activation restores autophagy, which is impaired by Meth administration. This occurs via restoration of the autophagy flux and, as assessed by ultrastructural morphometry, by preventing the dissipation of microtubule-associated protein 1 light chain 3 (LC3) from autophagy vacuoles to the cytosol, which is produced instead during Meth toxicity. These findings may have an impact in a variety of degenerative conditions characterized by NE deficiency along with autophagy impairment.


Microbiology ◽  
2014 ◽  
Vol 160 (11) ◽  
pp. 2387-2395 ◽  
Author(s):  
Hechun Jiang ◽  
Feifei Liu ◽  
Shizhu Zhang ◽  
Ling Lu

P-type Ca2+-transporting ATPases are Ca2+ pumps, extruding cytosolic Ca2+ to the extracellular environment or the intracellular Ca2+ store lumens. In budding yeast, Pmr1 (plasma membrane ATPase related), and Pmc1 (plasma membrane calcium-ATPase) cannot be deleted simultaneously for it to survive in standard medium. Here, we deleted two putative Ca2+ pumps, designated AnPmrA and AnPmcA, from Aspergillus nidulans, and obtained the mutants ΔanpmrA and ΔanpmcA, respectively. Then, using ΔanpmrA as the starting strain, the promoter of its anpmcA was replaced with the alcA promoter to secure the mutant ΔanpmrAalcApmcA or its anpmcA was deleted completely to produce the mutant ΔanpmrAΔpmcA. Different from the case in Saccharomyces cerevisiae, double deletion of anpmrA and anpmcA was not lethal in A. nidulans. In addition, deletion of anpmrA and/or anpmcA had produced growth defects, although overexpression of AnPmc1 in ΔanpmrAalcApmcA could not restore the growth defects that resulted from the loss of AnPmrA. Moreover, we found AnPmrA was indispensable for maintenance of normal morphogenesis, especially in low-Ca2+/Mn2+ environments. Thus, our findings suggest AnPmrA and AnPmcA might play important roles in growth, morphogenesis and cell wall integrity in A. nidulans in a different way from that in yeasts.


Vestnik ◽  
2021 ◽  
pp. 208-214
Author(s):  
Б.К. Кайрат ◽  
С.Т. Тулеуханов ◽  
В.П. Зинченко

Ионы Са являются основным мессенджером в регуляции физиологических функций клеток. Внутриклеточном пространстве ионы Ca могут свободно состоянии диффундироваться в различных частях цитоплазмы, в то же время значительное количество Ca в связанном виде накапливается в различных внутриклеточных депо или в составе кальций-связывающих белков. Регуляция физиологических процессов с ионами внутриклеточного Са происходит в диапазоне концентраций 10 М, тогда как концентрация Са во внеклеточном пространстве выше и составляет 10 М, для поддержании градиента концентраций в клетках имеются важные Са транспортирующие системы плазматической мембраны, эндоплазматического ретикулума и митохондрий. В нейронах функционируют внутриклеточные ферменты и белки плазматической мембраны для поддержания Са-гомеостаза и реализации механизмов внутриклеточной сигнализации для обеспечения жизнедеятельности в выживании клеток. Нарушение или гиперактивация одного или нескольких механизмов кальциевой сигнализации может привести к повреждению и гибели нейронов в случае отсутствия компенсаторных механизмов. Ca ions are a key messenger for the regulation of most of the physiological functions of cells. Inside the cell, Ca ions can freely diffuse in various parts of the cytoplasm, but a significant amount of Ca is also bound in various intracellular depots or in the form of calcium-binding proteins. The regulation of physiological processes by intracellular Ca ions occurs in the concentration range of 10 M, and the concentration of Ca in the extracellular space is higher and is 10 M, and to maintain this concentration gradient, cells have Ca-transporting systems of the plasma membrane, endoplasmic reticulum and mitochondria. In neurons, a large number of intracellular enzymes and plasma membrane proteins function to maintain Ca-homeostasis and implement intracellular signaling mechanisms to ensure vital activity in the survival of cells. Violation or hyperactivation of one or more mechanisms of calcium signaling can lead to cell damage and death in the absence of compensatory mechanisms.


1998 ◽  
Vol 275 (5) ◽  
pp. C1277-C1283 ◽  
Author(s):  
Martin Wilding ◽  
Gian Luigi Russo ◽  
Anthony Galione ◽  
Marcella Marino ◽  
Brian Dale

We report an ion channel in the plasma membrane of unfertilized oocytes of the ascidian Ciona intestinalis that is directly gated by the second messenger ADP-ribose. The ion channel is permeable to Ca2+ and Na+ and is characterized by a reversal potential between 0 and +20 mV and a unitary conductance of 140 pS. Preinjection of the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid (BAPTA) or antagonists of intracellular Ca2+ release channels into oocytes did not inhibit the ADP-ribose current, demonstrating that the channel is activated in a Ca2+-independent manner. Both the fertilization current and the current induced by the injection of nicotinamide nucleotides are blocked by nicotinamide, suggesting that the ADP-ribose channel is activated at fertilization in a nicotinamide-sensitive manner. These data suggest that ascidian sperm trigger the hydrolysis of nicotinamide nucleotides in the oocyte to ADP-ribose and that this mechanism is responsible for the production of the fertilization current.


Stroke ◽  
1983 ◽  
Vol 14 (1) ◽  
pp. 62-66 ◽  
Author(s):  
I Akiguchi ◽  
H Fukuyama ◽  
M Kameyama ◽  
T Koyama ◽  
H Kimura ◽  
...  

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