Binding of Paroxetine to the Serotonin Transporter in Membranes from Different Cells, Subcellular Fractions and Species

Cupello, A.; Albano, C.; Gatta, Elena; Scarrone, S.; Villa, E.; Zona, Gianluigi

doi:10.1007/s11064-008-9764-z

Cited by 9 publications

(12 citation statements)

References 21 publications

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“…Studies have found positive correlations for SLC6A4 kinetics between blood platelet and nerve endings, midbrain and brain synaptosomes, suggesting an association between peripheral and central SLC6A4 activity. [156][157][158]. Moreover, it is possible to use peripheral blood to detect psychiatric conditions involving central 5-HT alterations.…”

Section: Discussionmentioning

confidence: 99%

Looking beyond the DNA sequence: the relevance of DNA methylation processes for the stress–diathesis model of depression

Booij

Wang

Lévesque

et al. 2013

Phil. Trans. R. Soc. B

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The functioning of the hypothalamic–pituitary–adrenal (HPA) axis and serotonergic (5-HT) system are known to be intertwined with mood. Alterations in these systems are often associated with depression. However, neither are sufficient to cause depression in and of themselves. It is now becoming increasingly clear that the environment plays a crucial role, particularly, the perinatal environment. In this review, we posit that early environmental stress triggers a series of epigenetic mechanisms that adapt the genome and programme the HPA axis and 5-HT system for survival in a harsh environment. We focus on DNA methylation as it is the most stable epigenetic mark. Given that DNA methylation patterns are in large part set within the perinatal period, long-term gene expression programming by DNA methylation is especially vulnerable to environmental insults during this period. We discuss specific examples of genes in the 5-HT system (serotonin transporter) and HPA axis (glucocorticoid receptor and arginine vasopressin enhancer) whose DNA methylation state is associated with early life experience and may potentially lead to depression vulnerability. We conclude with a discussion on the relevance of studying epigenetic mechanisms in peripheral tissue as a proxy for those occurring in the human brain and suggest avenues for future research.

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Section: Discussionmentioning

confidence: 99%

Looking beyond the DNA sequence: the relevance of DNA methylation processes for the stress–diathesis model of depression

Booij

Wang

Lévesque

et al. 2013

Phil. Trans. R. Soc. B

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“…When evaluating the 5-HT concentration in blood, it should be taken in mind that in contrast to GnRH and DA, it is not only dissolved in plasma but mostly accumulated in platelets [95,96]. Therefore, these pools of 5-HT were evaluated separately.…”

Section: The Advanced Concept Of the Neuroendocrine Regulation In Ontmentioning

confidence: 99%

Developing Brain as an Endocrine Organ: A Paradoxical Reality

Ugrumov

2010

Neurochem Res

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The maintaining of homeostasis in the organism in response to a variable environment is provided by the highly hierarchic neuroendocrine-immune system. The crucial component of this system is the hypothalamus providing the endocrine regulation of key peripheral organs, and the adenohypophysis. In this case, neuron-derived signaling molecules (SM) are delivered to the blood vessels in hypothalamic "neurohaemal organs" lacking the blood-brain barrier (BBB), the posterior lobe of the pituitary and the median eminence. The release of SM to the blood vessels in most other brain regions is prohibited by BBB. According to the conventional concept, the development of the neuroendocrine system in ontogenesis begins with the "maturation" of peripheral endocrine glands which first are self-governed and then operate under the adenohypophysial control. Meantime, the brain maturation is under the control of SM secreted by endocrine glands of the developing organism and coming from the placenta and maternal organism. The hypothalamus is involved in the neuroendocrine regulation only after its full maturation that is followed by the conversion of the opened-looped neuroendocrine system to the closed-looped system as in adulthood. Neurons of the developing brain begin to secrete SM shortly after their origin and long before the establishment of specific interneuronal relations providing initially autocrine and paracrine morphogenetic influence on differentiating target neurons. Taking into account that the brain lacks BBB over this ontogenetic period, we hypothesized that it operates as the multipotent endocrine gland secreting SM to the general circulation and thereby providing the endocrine regulation of peripheral organs and the brain. The term "multipotent" means that the spectrum of the brain-derived circulating SM and their occupancy at the periphery in the developing organism should greatly exceed those in adulthood. In order to test this hypothesis, gonadotropin-releasing hormone (GnRH), dopamine (DA), and serotonin (5-hydroxytryptamine, 5-HT) were chosen as the markers of the presumptive endocrine function of the brain in ontogenesis. According to our data, the concentrations of GnRH, DA, and 5-HT in the rat general circulation during the perinatal period, i.e. before the establishment of BBB, was as high as those in the portal circulation in adulthood. The concentrations of circulating GnRH and DA dropped to almost undetectable level after the development of BBB suggesting their brain origin. This suggestion has been proven by showing an essential decrease of GnRH, DA, and 5-HT concentrations in general circulation of perinatal rats after microsurgical elimination of synthesizing neurons or the inhibition of specific syntheses in the brain before the establishment of BBB. GnRH, DA, and 5-HT apparently as dozens of other brain-derived SM appear to be capable of providing the endocrine influence on their peripheral targets like the adenohypophysis, gonads, kidney, heart, blood vessels, and the brain (endocrine autoregulat...

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“…Serotonin transporters are reported to be expressed in primary B-lymphocytes, 41 T-lymphocytes, 41 and mixed lymphocyte populations. 44,41,45,46,21 However, others have failed to detect (or have detected only small amounts of) SERT in B-lymphocytes 33,34 and T-lymphocytes. 30 Human lymphoblastoid cell lines, which are Epstein−Barr virusimmortalized B-lymphocytes, are also thought to express functional SERT and have been used to study human SERT gene variants.…”

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confidence: 99%

Serotonin Uptake Is Largely Mediated by Platelets versus Lymphocytes in Peripheral Blood Cells

Beikmann

Tomlinson²,

Rosenthal³

et al. 2012

ACS Chem. Neurosci.

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ABSTRACT:The serotonin transporter (SERT), a primary target for many antidepressants, is expressed in the brain and also in peripheral blood cells. Although platelet SERT function is well accepted, lymphocyte SERT function has not been definitively characterized. Due to their small size, platelets often are found in peripheral blood mononuclear cell preparations aimed at isolating lymphocytes, monocytes, and macrophages. The presence of different cells makes it difficult to assign SERT expression and function to specific cell types. Here, we use flow cytometry and IDT307, a monoamine transporter substrate that fluoresces after uptake into cells, to investigate SERT function in lymphocyte and platelet populations independently, as well as simultaneously without prior isolation. We find that murine lymphocytes exhibit temperature-dependent IDT307 transport but uptake is independent of SERT. Lack of measurable SERT function in lymphocytes was corroborated by chronoamperometry using serotonin as a substrate. When we examined rhesus and human mixed blood cell populations, we found that platelets, and not lymphocytes, were primary contributors to SERT function. Overall, these findings indicate that lymphocyte SERT function is minimal. Moreover, flow cytometry, in conjunction with the fluorescent transporter substrate IDT307, can be widely applied to investigate SERT in platelets from populations of clinical significance.

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Binding of Paroxetine to the Serotonin Transporter in Membranes from Different Cells, Subcellular Fractions and Species

Cited by 9 publications

References 21 publications

Looking beyond the DNA sequence: the relevance of DNA methylation processes for the stress–diathesis model of depression

Looking beyond the DNA sequence: the relevance of DNA methylation processes for the stress–diathesis model of depression

Developing Brain as an Endocrine Organ: A Paradoxical Reality

Serotonin Uptake Is Largely Mediated by Platelets versus Lymphocytes in Peripheral Blood Cells

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