5-Hydroxytryptamine–Mediated Neurotransmission Modulates Spontaneous and Vagal-Evoked Glutamate Release in the Nucleus of the Solitary Tract Effect of Uptake Blockade

Hosford, Patrick S.; Mifflin, Steve; Ramage, Andrew G.

doi:10.1124/jpet.113.211334

Cited by 19 publications

(21 citation statements)

References 36 publications

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“…The B3 region, and in particular the raphe magnus, receives massive projections from the dlPAG (Fardin et al, 1984) that, in turn, provides a significant set of serotonergic projection to the NTS (Schaffar et al, 1988;Thor and Helke, 1987). Thus dlPAG activation may be at the origin of serotonin release into the NTS, to ultimately activate presynaptic 5-HT 3a receptors (Hosford et al, 2014), as found previously (Bernard et al, 2008). The…”

supporting

confidence: 51%

A hypothalamo-midbrain-medullary pathway involved in the inhibition of the respiratory chemoreflex response induced by potassium cyanide in rodents

et al. 2018

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To cite this version:Tabinda Zafar, Charly Brouillard, Laurence Lanfumey, Caroline Sévoz-Couche. A hypothalamomidbrain-medullary pathway involved in the inhibition of the respiratory chemoreflex response induced by potassium cyanide in rodents.Neuropharmacology, Elsevier, 2017Elsevier, , 10.1016Elsevier, /j.neuropharm.2017 Accepted Manuscript A hypothalamo-midbrain-medullary pathway involved in the inhibition of the respiratory chemoreflex response induced by potassium cyanide in rodents This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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confidence: 51%

A hypothalamo-midbrain-medullary pathway involved in the inhibition of the respiratory chemoreflex response induced by potassium cyanide in rodents

et al. 2018

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“…While corticosterone inhibits human OCT3 with greater potency than OCT1 and OCT2, it is much less potent for PMAT than for OCT1‐3 ( Table ) . Due to the lack of a PMAT‐specific inhibitor, sensitivity to D22 but not to corticosterone has been used as an indirect approach in many cell and tissue studies to discern PMAT activity from those of the OCTs . Recently, we identified the fluorescent MPP + analog, IDT307, as a transportable substrate for PMAT and developed a fluorescence assay for rapid identification and characterization of PMAT inhibitors .…”

Section: Molecular and Functional Characteristics Of Pmatmentioning

confidence: 99%

The plasma membrane monoamine transporter (PMAT): Structure, function, and role in organic cation disposition

Wang

2016

Clin Pharma and Therapeutics

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Plasma membrane monoamine transporter (PMAT) is a new polyspecific organic cation transporter that transports a variety of biogenic amines and xenobiotic cations. Highly expressed in the brain, PMAT represents a major uptake2 transporter for monoamine neurotransmitters. At the blood–cerebrospinal fluid (CSF) barrier, PMAT is the principal organic cation transporter for removing neurotoxins and drugs from the CSF. Here I summarize our latest understanding of PMAT and its roles in monoamine uptake and xenobiotic disposition.

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“…Interestingly, in the present experiments in vivo and those in the slice (Hosford et al . ), these data indicate that SERT does function in the NTS, but is not involved in vagally evoked release of 5‐HT. This implies that PMAT must be located much nearer to the site of this evoked 5‐HT release than SERT.…”

Section: Discussionmentioning

confidence: 65%

“…; Wan & Browning, ; Hosford et al . ). The source of this 5‐HT release has not been determined; it may be from vagal afferent terminals and/or 5‐HT terminals within the NTS originating from other brain areas.…”

Section: Discussionmentioning

confidence: 97%

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Cardiovascular afferents cause the release of 5‐HT in the nucleus tractus solitarii; this release is regulated by the low‐ (PMAT) not the high‐affinity transporter (SERT)

Hosford

Millar

Ramage

2015

The Journal of Physiology

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Key pointsr The nucleus tractus solitarii (NTS) integrates visceral afferent information essential for cardiovascular haemostasis.r Using fast-cyclic voltammetry in anaesthetized rats, 5-HT (serotonin) release was detected in NTS in response to activation of these afferents.r Removal of 5-HT from the extracellular space is usually regulated by the low-capacity, high-affinity 5-HT transporter (5-HTT/SERT).r The present data demonstrate that 5-HT removal in the NTS is regulated by the plasma membrane monoamine transporter (PMAT), a high-capacity, low-affinity transporter.r The present data also demonstrate that the 5-HT released by afferent activation comes from at least two different sources. It is suggested that one of these sources is the afferents themselves.r These results demonstrate a physiological role for the low-affinity uptake transporter in the regulation of 5-HT concentration in NTS.Abstract The nucleus tractus solitarii (NTS) integrates inputs from cardiovascular afferents and thus is crucial for cardiovascular homeostasis. These afferents primarily release glutamate, although 5-HT has also been shown to play a role in their actions. Using fast-cyclic voltammetry, an increase in 5-HT concentrations (range 12-50 nM) could be detected in the NTS in anaesthetized rats in response to electrical stimulation of the vagus and activation of cardiopulmonary, chemo-and baroreceptor reflexes. This 5-HT signal was not potentiated by the serotonin transporter (SERT) or the noradrenaline transporter (NET) inhibitors citalopram and desipramine (1 mg kg −1 ). However, decynium-22 (600 μg kg −1 ), an organic cation 3 transporter (OCT3)/plasma membrane monoamine transporter (PMAT) inhibitor, increased the 5-HT signal by 111 ± 21% from 29 ± 10 nM. The effectiveness of these inhibitors was tested against the removal time of 5-HT and noradrenaline applied by microinjection to the NTS. Citalopram and decynium-22 attenuated the removal of 5-HT but not noradrenaline, whereas desipramine had the reverse action. The OCT3 inhibitor corticosterone (10 mg kg −1 ) had no effect. Blockade of glutamate receptors with topical kynurenate (10-50 nM) reduced the vagally evoked 5-HT signal by 50%, indicating that this release was from at least two sources. It is concluded that vagally evoked 5-HT release is under the regulation of the high-capacity, low-affinity transporter PMAT, not the low-capacity, high-affinity transporter SERT. This is the first demonstration that PMAT may be playing a physiological role in the regulation of 5-HT transmission and this could indicate that 5-HT is acting, in part, as a volume transmitter within the NTS.

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5-Hydroxytryptamine–Mediated Neurotransmission Modulates Spontaneous and Vagal-Evoked Glutamate Release in the Nucleus of the Solitary Tract Effect of Uptake Blockade

Cited by 19 publications

References 36 publications

A hypothalamo-midbrain-medullary pathway involved in the inhibition of the respiratory chemoreflex response induced by potassium cyanide in rodents

A hypothalamo-midbrain-medullary pathway involved in the inhibition of the respiratory chemoreflex response induced by potassium cyanide in rodents

The plasma membrane monoamine transporter (PMAT): Structure, function, and role in organic cation disposition

Cardiovascular afferents cause the release of 5‐HT in the nucleus tractus solitarii; this release is regulated by the low‐ (PMAT) not the high‐affinity transporter (SERT)

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