Brain Plasma Membrane Monoamine Transporter in Health and Disease

Vieira, Leticia Salvador; Wang, Joanne

doi:10.1007/164_2021_446

Cited by 15 publications

(14 citation statements)

References 98 publications

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“…In contrast, expression of OCT3 in whole hippocampal homogenates was lower in juveniles than adults, and in CA3 region of hippocampus, where chronoamperometry recordings were made, it did not differ between ages. Given that PMAT is the most efficient transporter of serotonin of the D22-sensitive transporters [ 13 ], our results align with the possibility that PMAT is a key driver of serotonin clearance in juveniles.…”

Section: Discussionsupporting

confidence: 82%

“…Organic cation transporter 3 (OCT3) and plasma membrane monoamine transporter (PMAT) are low-affinity, but high-capacity transporters of serotonin [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. We have shown that a sub-effective dose of the SSRI fluvoxamine, in conjunction with decynium-22 (D22, a blocker of OCTs and PMAT), which by itself does not have antidepressant-like effects, produces robust antidepressant-like effects in adult mice [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Faster Serotonin Clearance in CA3 Region of Hippocampus and Antidepressant-like Effect of Decynium-22 in Juvenile Mice Are Putatively Linked to Increased Plasma Membrane Monoamine Transporter Function: Implications for Efficacy of Antidepressants in Juveniles

Bowman

Gómez

Mitchell

et al. 2022

Cells

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Selective serotonin reuptake inhibitors (SSRIs) are less efficacious in treating depression in children than in adults. SSRIs block serotonin uptake via the high-affinity, low-capacity serotonin transporter. However, the low-affinity, high-capacity organic cation transporter 3 (OCT3) and plasma membrane monoamine transporter (PMAT) are emerging as important players in serotonin uptake. We hypothesized that OCT3 and/or PMAT are functionally upregulated in juveniles, thereby buffering SSRIs’ ability to enhance serotonergic neurotransmission. Unlike in adult mice, we found the OCT/PMAT blocker, decynium-22, to have standalone antidepressant-like effects in juveniles. Using in vivo high-speed chronoamperometry, we found that juveniles clear serotonin from the CA3 region of the hippocampus ~2-fold faster than adult mice. Cell density did not differ between ages, suggesting that faster serotonin clearance in juveniles is unrelated to faster diffusion through the extracellular matrix. Western blot and immunohistochemistry showed that juvenile mice have modestly greater expression of PMAT than adults, whereas OCT3 expression in the CA3 region of the hippocampus was similar between ages. Together, these data suggest that faster serotonin clearance and antidepressant-like effects of decynium-22 in juvenile mice may be due to functionally upregulated PMAT. Faster serotonin clearance via PMAT in juveniles may contribute to reduced therapeutic efficacy of SSRIs in children relative to adults.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Faster Serotonin Clearance in CA3 Region of Hippocampus and Antidepressant-like Effect of Decynium-22 in Juvenile Mice Are Putatively Linked to Increased Plasma Membrane Monoamine Transporter Function: Implications for Efficacy of Antidepressants in Juveniles

Bowman

Gómez

Mitchell

et al. 2022

Cells

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“…The transport of small organic cations by PMAT is electrogenic and pH sensitive (Duan and Wang, 2010;Zhou et al, 2010). PMAT is highly expressed in the brain and also has varied expression in the kidney, small intestine, and the heart (Dahlin et al, 2007;Duan and Wang, 2013;Vieira and Wang, 2021;Xia et al, 2007;Zhou et al, 2007). Furthermore, PMAT was identified in an exploratory study as one of the top 25 membrane protein genes overexpressed in neuroblastoma tumor samples (Orentas et al, 2012).…”

Section: Hoct1 and Hoct3 In Tissue Uptake Of Mibgmentioning

confidence: 99%

“…Brain, kidney, small intestine, heart, liver, skeletal muscle (Dahlin et al, 2007;Duan and Wang, 2013;Engel et al, 2004;Vieira and Wang, 2021;Wagner et al, 2016;Wang, 2016;Xia et al, 2007; MATE1 (SLC47A1) 17.7 ± 10.9 a Electroneutral (H + /OC + exchange) Kidney, liver, skeletal muscle (International Transporter Consortium et al, 2010;López Quiñones et al, 2020;Masuda et al, 2006;Otsuka et al, 2005…”

Section: Footnotesmentioning

confidence: 99%

Clinical Applications and the Roles of Transporters in Disposition, Tumor Targeting, and Tissue Toxicity of meta-Iodobenzylguanidine

2022

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Transporters on the plasma membrane of tumor cells are promising molecular "Trojan horses" to deliver drugs and imaging agents into cancer cells. Radioiodine-labeled metaiodobenzylguanidine (mIBG) is used as a diagnostic agent ( 123 I-mIBG) and a targeted radiotherapy ( 131 I-mIBG) for neuroendocrine cancers. mIBG enters cancer cells through the norepinephrine transporter (NET) where the radioactive decay of 131 I causes DNA damage, cell death, and tumor necrosis. mIBG is predominantly eliminated unchanged by the kidney.Despite its selective uptake by neuroendocrine tumors, mIBG accumulates in several normal tissues and leads to tissue-specific radiation toxicities. Emerging evidences suggest that the polyspecific organic cation transporters play important roles in systemic disposition and tissuespecific uptake of mIBG. In particular, human organic cation transporter 2 (hOCT2) and toxin extrusion proteins 1 and 2-K (hMATE1/2-K) likely mediate renal secretion of mIBG whereas hOCT1 and hOCT3 may contribute to mIBG uptake into normal tissues such as the liver, salivary glands, and heart. This mini-review focuses on the clinical applications of mIBG in neuroendocrine cancers and the differential roles of NET, OCT and MATE transporters in mIBG disposition, response and toxicity. Understanding the molecular mechanisms governing mIBG transport in cancer and normal cells is a critical step for developing strategies to optimize the efficacy of 131 I-mIBG while minimizing toxicity in normal tissues.

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“…Although SERT expression in astrocytes has been reported by several groups (Inazu et al, 2001; Kubota et al, 2001; Malynn et al, 2013), these findings remain limited and require further validation. In addition to SERT, it has been shown that organic cation transporters (Baganz et al, 2008; Schmitt et al, 2003), plasma membrane monoamine transporters (Vieira & Wang, 2021; Zhou et al, 2007), dopamine transporters (Daws, 2009; Zhou et al, 2002), and norepinephrine transporters (Daws, 2009; Daws et al, 1998) are also involved in the serotonin clearance process from extracellular space. These “non‐traditional” serotonin‐clearing proteins play an important role when extracellular serotonin levels are excessive, especially as a complementary mechanism when SERT function is deficient (Baganz et al, 2008; Daws, 2009; Pan et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Techniques for in vivo serotonin detection in the brain: State of the art

Zhao

Piatkevich

2023

Journal of Neurochemistry

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Neuronal circuits in the brain that utilize the neurotransmitter serotonin are essential to the regulation of mood and emotional expression. Disruptions in serotonin signaling underlie neuropsychiatric conditions such as depression and anxiety. However, the cellular mechanisms that regulate serotonergic signaling in the brain in healthy and diseased states remain to be better understood. In particular, as more is learned about serotonin in the brain, we recognize an urgent need to develop techniques capable of mapping its complex spatiotemporal dynamics in awake, behaving animals.Notably, analytical methods to detect serotonin in situ, including tomography, are widely used but still recognized as limited in terms of their spatiotemporal resolution, their methodological caveats, and their technical limitations when cross-referenced with behavioral studies. To overcome such limitations, genetically encoded serotonin indicators were developed, leading to the introduction of novel imaging modalities that enable researchers to achieve remarkable spatiotemporal resolution in the study of serotonergic circuits in preclinical models of neuropsychiatric disorders.These novel approaches, while remarkably powerful, are also not without limitations.Here, we review the current techniques for detecting and quantifying serotonin in vivo within the brain and discuss how novel approaches such as genetically encoded serotonin indicators will lead to new insights into the roles of serotonergic circuits in health and disease.

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Brain Plasma Membrane Monoamine Transporter in Health and Disease

Cited by 15 publications

References 98 publications

Faster Serotonin Clearance in CA3 Region of Hippocampus and Antidepressant-like Effect of Decynium-22 in Juvenile Mice Are Putatively Linked to Increased Plasma Membrane Monoamine Transporter Function: Implications for Efficacy of Antidepressants in Juveniles

Faster Serotonin Clearance in CA3 Region of Hippocampus and Antidepressant-like Effect of Decynium-22 in Juvenile Mice Are Putatively Linked to Increased Plasma Membrane Monoamine Transporter Function: Implications for Efficacy of Antidepressants in Juveniles

Clinical Applications and the Roles of Transporters in Disposition, Tumor Targeting, and Tissue Toxicity of meta-Iodobenzylguanidine

Techniques for in vivo serotonin detection in the brain: State of the art

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