Control of Renal Factors in Plasma Homovanillic Acid Measurements

Amin, Maha; Stroe, Mariana; Kahn, Melvin; Knott, P. J.; Kahn, Moshe; Davidson, Michael

doi:10.1016/s0893-133x(97)00142-5

Cited by 6 publications

(2 citation statements)

References 9 publications

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“…Since 5-HIAA is an organic acid, it cannot cross biological membranes by passive diffusion; instead, it must exit the cells via an efflux membrane transport system. Active mechanisms of 5-HIAA excretion in the human and rat brain and kidney were reported to be probenecid-dependent [ 13 – 16 ], indicating the involvement of an organic anion transporter (OAT) [ 35 ] and/or multidrug resistance-associated protein 2 (MRP2) [ 37 ]. To test this hypothesis, we investigated the effects of the organic anion transporter inhibitor, probenecid, and the MRP2 inhibitor, MK-571, on 5-HT clearance in placental explants and trophoblast cells.…”

Section: Discussionmentioning

confidence: 99%

“…It is, therefore, essential for cells producing 5-HIAA to regulate the homeostasis of this metabolite and control its excretion for detoxication purposes. In the brain and kidney, probenecid-dependent transporter(s) have been suggested to efflux 5-HIAA from the cells [ 13 – 16 ]. No such detoxification mechanism has yet been identified in the placenta, however.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of a human placental clearance system to regulate serotonin levels in the fetoplacental unit

Staud,

Pan,

Karahoda

et al. 2023

Reprod Biol Endocrinol

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Background Serotonin (5-HT) is a biogenic monoamine with diverse functions in multiple human organs and tissues. During pregnancy, tightly regulated levels of 5-HT in the fetoplacental unit are critical for proper placental functions, fetal development, and programming. Despite being a non-neuronal organ, the placenta expresses a suite of homeostatic proteins, membrane transporters and metabolizing enzymes, to regulate monoamine levels. We hypothesized that placental 5-HT clearance is important for maintaining 5-HT levels in the fetoplacental unit. We therefore investigated placental 5-HT uptake from the umbilical circulation at physiological and supraphysiological levels as well as placental metabolism of 5-HT to 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA efflux from trophoblast cells. Methods We employed a systematic approach using advanced organ-, tissue-, and cellular-level models of the human placenta to investigate the transport and metabolism of 5-HT in the fetoplacental unit. Human placentas from uncomplicated term pregnancies were used for perfusion studies, culturing explants, and isolating primary trophoblast cells. Results Using the dually perfused placenta, we observed a high and concentration-dependent placental extraction of 5-HT from the fetal circulation. Subsequently, within the placenta, 5-HT was metabolized to 5-hydroxyindoleacetic acid (5-HIAA), which was then unidirectionally excreted to the maternal circulation. In the explant cultures and primary trophoblast cells, we show concentration- and inhibitor-dependent 5-HT uptake and metabolism and subsequent 5-HIAA release into the media. Droplet digital PCR revealed that the dominant gene in all models was MAO-A, supporting the crucial role of 5-HT metabolism in placental 5-HT clearance. Conclusions Taken together, we present transcriptional and functional evidence that the human placenta has an efficient 5-HT clearance system involving (1) removal of 5-HT from the fetal circulation by OCT3, (2) metabolism to 5-HIAA by MAO-A, and (3) selective 5-HIAA excretion to the maternal circulation via the MRP2 transporter. This synchronized mechanism is critical for regulating 5-HT in the fetoplacental unit; however, it can be compromised by external insults such as antidepressant drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of a human placental clearance system to regulate serotonin levels in the fetoplacental unit

Staud,

Pan,

Karahoda

et al. 2023

Reprod Biol Endocrinol

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Effect of Basal Ganglia Injury on Central Dopamine Activity in Gulf War Syndrome

Haley¹,

Fleckenstein

Marshall

et al. 2000

Arch Neurol

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Plasma homovanillic acid correlates inversely with history of childhood trauma in personality disordered and healthy control adults

Lee

Coccaro

2010

J Neural Transm

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Studies of the cerebrospinal fluid (CSF) level of the dopamine metabolite, homovanillic acid (HVA), suggest a relationship between CSF HVA concentration and history of childhood trauma. In this study, the authors test the hypothesis that this relationship is also present using peripheral levels of HVA in healthy volunteers and in personality disordered subjects. 68 personality disordered (PD) and healthy control (HC) subjects were chosen, in whom morning basal plasma HVA (pHVA) concentrations and an assessment of childhood trauma were obtained. History of childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). A significant inverse correlation was found between CTQ Total scores and pHVA concentration across all subjects. In addition, pHVA was lower, and CTQ scores were higher, in PD as compared with HC subjects. Correlations with other personality and behavioral measures were not statistically significant. The data suggest that pHVA concentrations are inversely correlated with history of childhood trauma and that variability in this index of dopamine function may be affected by the history of childhood trauma in healthy and personality disordered subjects.

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Control of Renal Factors in Plasma Homovanillic Acid Measurements

Cited by 6 publications

References 9 publications

Characterization of a human placental clearance system to regulate serotonin levels in the fetoplacental unit

Characterization of a human placental clearance system to regulate serotonin levels in the fetoplacental unit

Effect of Basal Ganglia Injury on Central Dopamine Activity in Gulf War Syndrome

Plasma homovanillic acid correlates inversely with history of childhood trauma in personality disordered and healthy control adults

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