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Melatonin inhibits SERT mediated 5‐HT uptake in human and mouse derived platelets and synaptosomes
Author(s) -
Thompson Brent,
Hill-Kapturczak Nathalie,
Javors Martin
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb580
Subject(s) - melatonin , platelet , endocrinology , serotonin , medicine , pineal gland , serotonergic , circadian rhythm , serotonin transporter , biology , extracellular , serotonin plasma membrane transport proteins , 5 ht receptor , chemistry , receptor , microbiology and biotechnology
Melatonin is a hormone present in most organisms from bacteria to mammals. A circadian cycle of its release from the pineal gland into the blood and CSF is thought to be involved in a variety of normal and abnormal human behaviors such as sleep, epilepsy and autism. The serotonin transporter (SERT) can be found in multiple cell types including neurons, platelets, lymphocytes and intestinal epithelial cells where its principal function is to regulate the concentration of extracellular serotonin (5HT). Dysregulation of serotonergic signaling has been linked with numerous psychiatric and neurodevelopmental disorders. Melatonin has been shown to inhibit SERT function in a non‐competitive manner with a diurnal variation in responsiveness. Interestingly, a circadian rhythm of SERT function in human platelets has been shown to run counter to the concentration of melatonin in plasma leading to the hypothesis that melatonin may in part regulate SERT activity in human platelets and neurons. In these preliminary studies, we have characterized the effect of melatonin on 5HT uptake in platelets and synaptosomes derived from both human and mouse and have demonstrated that melatonin inhibits SERT mediated 5‐HT transport with inhibitory constants in the mM range.