Norepinephrine triggers Ca2+-dependent exocytosis of 5-hydroxytryptamine from rat pinealocytes in culture.
Hiroshi Yamada,Mitsuko Hayashi,Shunsuke Uehara,Mika Kinoshita,Akiko Muroyama,Masami Watanabe,Koji Takei,Yoshinori Moriyama +7 more
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TL;DR: It is shown that upon stimulation of a adrenoceptors pinealocytes secrete 5‐HT through a Ca2+‐dependent exocytotic mechanism, which is distinct from the exocyTosis of synaptic‐like microvesicles.
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Abstract: 5-Hydroxytryptamine (5-HT) is a precursor and a putative modulator for melatonin synthesis in mammalian pinealocytes. 5-HT is present in organelles distinct from l-glutamate-containing synaptic-like microvesicles as well as in the cytoplasm of pinealocytes, and is secreted upon stimulation by norepinephrine (NE) to enhance serotonin N-acetyltransferase activity via the 5-HT2 receptor. However, the mechanism underlying the secretion of 5-HT from pinealocytes is unknown. In this study, we show that NE-evoked release of 5-HT is largely dependent on Ca2+ in rat pinealocytes in culture. Omission of Ca2+ from the medium and incubation of pineal cells with EGTA-tetraacetoxymethyl-ester inhibited by 59 and 97% the NE-evoked 5-HT release, respectively. Phenylephrine also triggered the Ca2+-dependent release of 5-HT, which was blocked by phentolamine, an α antagonist, but not by propranolol, a β antagonist. Botulinum neurotoxin type E cleaved 25 kDa synaptosomal-associated protein and inhibited by 50% of the NE-evoked 5-HT release. Bafilomycin A1, an inhibitor of vacuolar H+-ATPase, and reserpine and tetrabenazine, inhibitors of vesicular monoamine transporter, all decreased the storage of vesicular 5-HT followed by inhibition of the NE-evoked 5-HT release. Agents that trigger l-glutamte exocytosis such as acetylcholine did not trigger any Ca2+-dependent 5-HT release. Vice versa neither NE nor phenylephrine caused synaptic-like microvesicle-mediated l-glutamate exocytosis. These results indicated that upon stimulation of a adrenoceptors pinealocytes secrete 5-HT through a Ca2+-dependent exocytotic mechanism, which is distinct from the exocytosis of synaptic-like microvesicles.
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Citations
Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters
TL;DR: The aim of this review is to gather together early and recent data on the effects of the nonadrenergic transmitters on modulation of melatonin synthesis, which reveals the variety of inputs that can be integrated by the pineal gland; what elements are crucial to deliver the very precise timing information to the organism.
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Botulinum toxins--cause of botulism and systemic diseases?
TL;DR: In vivo actions of different botulinum toxins after their entry into the organism may contribute to the onset of different diseases of hitherto cryptogenic origin.
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NAADP receptors mediate calcium signaling stimulated by endothelin-1 and norepinephrine in renal afferent arterioles.
TL;DR: It is concluded that NAADP receptors contribute to both ET-1- and NE-induced [Ca(2+)](i) responses in afferent arterioles, an effect likely dependent on acidic vesicle, possibly involving lysosome, signaling in VSMC in the renal microcirculation.
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Section III. The norepinephrine system.
TL;DR: The chapter discusses the interactions of norepinephrine with transmitters such as glutamate and gamma–aminobutyric acid (GABA) and the interactions between the NE system and tropins and cytokines are discussed.
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Serotonin modulates melatonin synthesis as an autocrine neurotransmitter in the pineal gland.
TL;DR: In this paper, the pineal gland secretes 5-hydroxytryptamine (5-HT, serotonin) via a decynium-22-sensitive equilibrative plasma membrane monoamine transporter instead of by typical exocytotic quantal secretion.
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The melatonin rhythm-generating enzyme: molecular regulation of serotonin N-acetyltransferase in the pineal gland.
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TL;DR: The variety of mechanisms that have evolved among vertebrates to achieve the same goal-a rhythm in melatonin-underlines the important role melatonin plays as the hormonal signal of environmental lighting in vertebrates.
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Melatonin biosynthesis in the mammalian pineal gland.
TL;DR: A major aspect of the temporal control of melatonin production is the programmed down-regulation of responses to noradrenergic stimulation once the initial surge of c-AMP is produced.
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Rhythmic Transcription: The Molecular Basis of Circadian Melatonin Synthesis
TL;DR: The molecular mechanisms involved in rhythmic synthesis of melatonin synthesis involve the CREM gene, which encodes transcription factors responsive to activation of the cAMP signalling pathway, and cAMP-responsive activator transcription factors CREB and ATF1 and the repressor ICER, which are highly conserved in the chick.
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Alpha 1-adrenoceptor activation elevates cytosolic calcium in rat pinealocytes by increasing net influx.
TL;DR: The data indicate that pinealocyte [Ca2+]i may be influenced by mechanisms regulated by alpha 1-adrenoceptors, voltage-dependent Ca2+ channels, and perhaps a Na+/Ca 2+ exchange mechanism stimulated by ouabain.
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