Serotonergic Receptors as Targets for Pharmacotherapy

Kirk, E.; Giordano, James; Anderson, Ross S.

doi:10.1097/01376517-199706000-00007

Cited by 4 publications

(5 citation statements)

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“…Expression of transporters in chick is asymmetric, and thus may be expected to differentially regulate the availability of intracellular and extracellular 5-HT on the left versus right sides of Hensen's node. Since storage of serotonin in vesicles prevents catabolism by MAO prior to synaptic release [Kirk et al, 1997], VMAT activity may interact with the rightsided MAO expression [Fukumoto et al, 2005] to precisely control 5-HT levels. The function of SERT can increase cytoplasmic 5-HT but also reduce the availability of serotonin to neighboring cells.…”

Section: Discussionmentioning

confidence: 99%

“…To avoid degradation and provide for vesicular release, 5-HT is transported into vesicles through the action of the vesicular monoamine transporter (VMAT) [Kirk et al, 1997]. VMAT (VMAT2 in neurons, and VMAT1 in other tissues) uses proton gradients generated by the V-ATPase [Harvey, 1992] to drive transport exchanging two protons in the lumen of the vesicle for one monoamine in the cytoplasm [Knoth, 1981a, b;Kanner, 1987;Edwards, 1992].…”

Section: Introductionmentioning

confidence: 99%

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Serotonin Transporter Function Is an Early Step in Left-Right Patterning in Chick and Frog Embryos

Fukumoto

Blakely²,

Levin³

2005

Dev Neurosci

108

101

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The neurotransmitter serotonin has been shown to regulate a number of embryonic patterning events in addition to its crucial role in the nervous system. Here, we examine the role of two serotonin transporters, the plasma membrane serotonin transporter (SERT) and the vesicular monoamine transporter (VMAT), in embryonic left-right asymmetry. Pharmacological or genetic inhibitors of either SERT or VMAT specifically randomized the laterality of the heart and viscera in Xenopus embryos. This effect takes place during cleavage stages, and is upstream of the left-sided gene XNR-1. Targeted microinjection of an SERT-dominant negative construct confirmed the necessity for SERT function in embryonic laterality and revealed that the descendants of the right ventral blastomere are the most dependant upon SERT signaling in left-right patterning. Moreover, the importance of SERT and VMAT in laterality is conserved in chick embryos, being upstream of the early left-sided gene Shh. Endogenous transcripts of SERT and VMAT are expressed from the initiation of the primitive streak in chick and are asymmetrically expressed in Hensen’s node. Taken together our data characterize two new right-sided markers in chick gastrulation, identify a novel, early component of the left-right pathway in two vertebrate species, and reveal a new biological role for serotonin transport.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serotonin Transporter Function Is an Early Step in Left-Right Patterning in Chick and Frog Embryos

Fukumoto

Blakely²,

Levin³

2005

Dev Neurosci

108

101

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“…The serotonin pathway [Cooper et al, 1996] includes enzymes which synthesize 5-HT from the essential amino acid L -tryptophan, membrane receptors, which transduce the serotonin signal into different downstream cellular events (5-HT 1-7 ), and a system for enzymatic degradation of 5-HT via monoamine oxidase (MAO) [Gershon et al, 1990;Kirk et al, 1997]. Many cell types also possess a system of storage and release of 5-HT by vesicles, and a plasma membrane transporter (SERT) that imports extracellular 5-HT into the cytoplasm.…”

Section: Introductionmentioning

confidence: 99%

Of Minds and Embryos: Left-Right Asymmetry and the Serotonergic Controls of Pre-Neural Morphogenesis

Levin¹,

2006

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Serotonin is a clinically important neurotransmitter regulating diverse aspects of cognitive function, sleep, mood, and appetite. Increasingly, it is becoming appreciated that serotonin signaling among non-neuronal cells is a novel patterning mechanism existing throughout diverse phyla. Here, we review the evidence implicating serotonergic signaling in embryonic morphogenesis, including gastrulation, craniofacial and bone patterning, and the generation of left-right asymmetry. We propose two models suggesting movement of neurotransmitter molecules as a novel mechanism for how bioelectrical events may couple to downstream signaling cascades and gene activation networks. The discovery of serotonin-dependent patterning events occurring long before the development of the nervous system opens exciting new avenues for future research in evolutionary, developmental, and clinical biology.

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“…Serotonin is a monoamine synthesized intracellularly from L-tryptophan, released, and later degraded via monoamine oxidase action ( Kirk et al, 1997 ; Sahu et al, 2018 ). The serotonin signaling is transduced to subcellular events by specific membrane receptors of different classes.…”

Section: Serotonin Signaling Components Are Present In Craniofacial Tissuesmentioning

confidence: 99%

Depression and Antidepressants During Pregnancy: Craniofacial Defects Due to Stem/Progenitor Cell Deregulation Mediated by Serotonin

Sánchez

Juárez-Balarezo

Olhaberry

et al. 2021

Front. Cell Dev. Biol.

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Depression is a common and debilitating mood disorder that increases in prevalence during pregnancy. Worldwide, 7 to 12% of pregnant women experience depression, in which the associated risk factors include socio-demographic, psychological, and socioeconomic variables. Maternal depression could have psychological, anatomical, and physiological consequences in the newborn. Depression has been related to a downregulation in serotonin levels in the brain. Accordingly, the most commonly prescribed pharmacotherapy is based on selective serotonin reuptake inhibitors (SSRIs), which increase local serotonin concentration. Even though the use of SSRIs has few adverse effects compared with other antidepressants, altering serotonin levels has been associated with the advent of anatomical and physiological changes in utero, leading to defects in craniofacial development, including craniosynostosis, cleft palate, and dental defects. Migration and proliferation of neural crest cells, which contribute to the formation of bone, cartilage, palate, teeth, and salivary glands in the craniofacial region, are regulated by serotonin. Specifically, craniofacial progenitor cells are affected by serotonin levels, producing a misbalance between their proliferation and differentiation. Thus, it is possible to hypothesize that craniofacial development will be affected by the changes in serotonin levels, happening during maternal depression or after the use of SSRIs, which cross the placental barrier, increasing the risk of craniofacial defects. In this review, we provide a synthesis of the current research on depression and the use of SSRI during pregnancy, and how this could be related to craniofacial defects using an interdisciplinary perspective integrating psychological, clinical, and developmental biology perspectives. We discuss the mechanisms by which serotonin could influence craniofacial development and stem/progenitor cells, proposing some transcription factors as mediators of serotonin signaling, and craniofacial stem/progenitor cell biology. We finally highlight the importance of non-pharmacological therapies for depression on fertile and pregnant women, and provide an individual analysis of the risk–benefit balance for the use of antidepressants during pregnancy

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Serotonergic Receptors as Targets for Pharmacotherapy

Cited by 4 publications

References 0 publications

Serotonin Transporter Function Is an Early Step in Left-Right Patterning in Chick and Frog Embryos

Serotonin Transporter Function Is an Early Step in Left-Right Patterning in Chick and Frog Embryos

Of Minds and Embryos: Left-Right Asymmetry and the Serotonergic Controls of Pre-Neural Morphogenesis

Depression and Antidepressants During Pregnancy: Craniofacial Defects Due to Stem/Progenitor Cell Deregulation Mediated by Serotonin

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