The role of central 5‐HT₃ receptors in vagal reflex inputs to neurones in the nucleus tractus solitarius of anaesthetized rats

Abstract

)in96of106 neurones tested and in all 17 neurones tested the increase in activity (3.4 ± 1.1 to 7.0 ± 1.9 spikes s −1 ) was significantly attenuated (3.0 ± 0.9 to 3.8 ± 1.1 spikes s −1 ) by the selective 5-HT 3 receptor antagonist granisetron. Ionophoretic application of PBG potentiated responses to vagus nerve and cardiopulmonary afferent stimulation, and granisetron significantly attenuated this cardiopulmonary input (20.2 ± 5.7 to 10.6 ± 4.1 spikes burst −1 ) in 9 of 10 neurones tested. Ionophoretic application of AMPA and NMDA also excited NTS neurones and these excitations could be selectively antagonized by the non-NMDA and NMDA receptor antagonists DNQX and AP-5, respectively. At these selective currents, DNQX and AP-5 also attenuated PBG-and cardiopulmonary input-evoked increases in NTS activity. These data are consistent with the hypothesis that vagal inputs, including non-myelinated cardiopulmonary inputs to the NTS, utilize a 5-HT-containing pathway which activates 5-HT 3 receptors. This excitatory response to 5-HT 3 receptor activation may be partly a direct postsynaptic action but part may also be due to facilitation of the release of glutamate which in turn acts on either non-NMDA or NMDA receptors to evoke excitation.

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

“…Further, the NTS has the densest expression in the brain of the only ionotropic 5-HT receptor, the 5-HT 3 receptor. These receptors are found mainly on vagal afferent terminals (Leslie et al, 1990;Pratt and Bowery, 1989), and their blockade attenuates vagal afferent excitation of NTS neurons (Ramage and Mifflin, 1998;Jeggo et al, 2005). These 5-HT 3 receptors cause excitation of NTS neurons via the release of glutamate (Jeggo et al, 2005).…”

“…These receptors are found mainly on vagal afferent terminals (Leslie et al, 1990;Pratt and Bowery, 1989), and their blockade attenuates vagal afferent excitation of NTS neurons (Ramage and Mifflin, 1998;Jeggo et al, 2005). These 5-HT 3 receptors cause excitation of NTS neurons via the release of glutamate (Jeggo et al, 2005). This has also been confirmed in the NTS slice in the presence of tetrodotoxin (TTX) and bicuculline, in which the frequency of glutamatergic miniature excitatory postsynaptic currents (mEPSCs) was attenuated by blockade of 5-HT 3 receptors (Wan and Browning, 2008).…”

GABA in nucleus tractus solitarius participates in electroacupuncture modulation of cardiopulmonary bradycardia reflex

“…Under these conditions both spinal and vagal afferent pathways are stimulated to lower blood pressure through sympathetic withdrawal and increased parasympathetic outflow (40). Several medullary nuclei, including the caudal ventrolateral medulla (cVLM), rVLM, and nucleus ambiguus contribute to the modulatory actions of EA through GABA mechanisms (38).Activation of cardiopulmonary vagal afferents by prostaglandin E2 2 , veratrum alkaloids, serotonin (5-HT), capsaicin, or intravenous phenylbiguanide (PBG) elicits decreases in heart rate and blood pressure through the Bezold-Jarisch reflex (6,8,20). Intravenous PBG stimulates cardiopulmonary serotonin (5-HT 3 ) afferent endings projecting to supraspinal regions to evoke hypotension and bradycardia.…”

“…Activation of cardiopulmonary vagal afferents by prostaglandin E2 2 , veratrum alkaloids, serotonin (5-HT), capsaicin, or intravenous phenylbiguanide (PBG) elicits decreases in heart rate and blood pressure through the Bezold-Jarisch reflex (6,8,20). Intravenous PBG stimulates cardiopulmonary serotonin (5-HT 3 ) afferent endings projecting to supraspinal regions to evoke hypotension and bradycardia.…”

Synthesis and Pharmacological Evaluation of [11C]Granisetron and [18F]Fluoropalonosetron as PET Probes for 5-HT3 Receptor Imaging

“…8 Electrophysiology provides support for a predominantly presynaptic localization of these receptors, although some postsynaptic 5-HT3 receptors are also reported. [14][15][16][17] Expression in other regions of the brain is usually low (see ref 18 for a comprehensive review). In the periphery, 5-HT3 receptors are found in vagal afferent nerve fibers from the heart and GI tract which are responsible for the Bezold-Jarisch reflex and initiation of vomiting reflex, respectively.…”