title: 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).
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.
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Hosford
authors.forename: Julian
authors.initials: J
authors.lastname: Millar
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Ramage
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004558:Electric Stimulation; D033705:Equilibrative Nucleoside Transport Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology
chemical_list: D015283:Citalopram; D003891:Desipramine; D033705:Equilibrative Nucleoside Transport Proteins; D007736:Kynurenic Acid; D009638:Norepinephrine; D011804:Quinolines; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C100254:pseudoisocyanine