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Serotonin modulates melatonin synthesis as an autocrine neurotransmitter in the pineal gland
- Source :
- Proc Natl Acad Sci U S A
- Publication Year :
- 2021
-
Abstract
- 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 Ca(2+) rise that was blocked by RS-102221, an antagonist of 5-HT(2C) 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.
- Subjects :
- Male
medicine.medical_specialty
endocrine system
Serotonin
Adrenergic receptor
Ligands
Pineal Gland
Exocytosis
Pinealocyte
Melatonin
Rats, Sprague-Dawley
chemistry.chemical_compound
Pineal gland
GTP-Binding Proteins
Internal medicine
N-Acetylserotonin
medicine
Animals
Neurotransmitter
5-HT receptor
Neurotransmitter Agents
Multidisciplinary
Biological Sciences
Rats
Up-Regulation
Endocrinology
medicine.anatomical_structure
chemistry
Ion Channel Gating
hormones, hormone substitutes, and hormone antagonists
medicine.drug
Signal Transduction
Subjects
Details
- ISSN :
- 10916490
- Volume :
- 118
- Issue :
- 43
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....22c0c4b8bc380d082e1e2e7575680a49