Diana Oskutyte1, David Jordan, Andrew G Ramage. 1. Research Department of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, London, UK.
Abstract
BACKGROUND AND PURPOSE: Central 5-hydroxytryptamine (5-HT)-containing pathways utilizing 5-HT(7) receptors are known to be critical for the mediation of cardiovascular reflexes. The nucleus tractus solitarius (NTS) is a site involved in the integration of cardiovascular afferent information. The present experiments examined the involvement of the 5-HT(7) receptor in the processing of cardiovascular reflexes in the NTS. EXPERIMENTAL APPROACH: In anaesthetized rats extracellular recordings were made from 104 NTS neurones that were excited by electrical stimulation of the vagus nerve and/or activation of cardiopulmonary afferents. Drugs were applied ionophoretically in the vicinity of these neurones. KEY RESULTS: The non-selective 5-HT(7) receptor agonist 5-carboxamidotryptamine maleate (5-CT) applied to 78 neurones increased the firing rate in 18 by 59% and decreased it in 38 neurones by 47%. Similarly, the 5-HT(1A) agonist 8-OH-DPAT applied to 20 neurones had an excitatory (8), inhibitory (7) or no effect (5) on the 20 neurones tested. In the presence of the 5-HT(7) antagonist SB 258719 the 5-CT excitation was attenuated. Furthermore, the excitatory response of NTS neurones evoked by electrical stimulation of the vagus nerve or activation of cardiopulmonary afferents with intra atrial phenylbiguanide was attenuated by SB 258719. The inhibitory action of 5-CT was unaffected by SB 258719 and the 5-HT(1A) antagonist WAY-100635. WAY-100635 failed to have any effect on 5-CT and vagal afferent-evoked excitations. CONCLUSIONS AND IMPLICATIONS: Vagal afferent-evoked excitation of NTS neurones can be blocked by SB 258719, a selective 5-HT(7) antagonist. This observation further supports the involvement of 5-HT neurotransmission in NTS afferent processing.
BACKGROUND AND PURPOSE: Central 5-hydroxytryptamine (5-HT)-containing pathways utilizing 5-HT(7) receptors are known to be critical for the mediation of cardiovascular reflexes. The nucleus tractus solitarius (NTS) is a site involved in the integration of cardiovascular afferent information. The present experiments examined the involvement of the 5-HT(7) receptor in the processing of cardiovascular reflexes in the NTS. EXPERIMENTAL APPROACH: In anaesthetized rats extracellular recordings were made from 104 NTS neurones that were excited by electrical stimulation of the vagus nerve and/or activation of cardiopulmonary afferents. Drugs were applied ionophoretically in the vicinity of these neurones. KEY RESULTS: The non-selective 5-HT(7) receptor agonist 5-carboxamidotryptamine maleate (5-CT) applied to 78 neurones increased the firing rate in 18 by 59% and decreased it in 38 neurones by 47%. Similarly, the 5-HT(1A) agonist 8-OH-DPAT applied to 20 neurones had an excitatory (8), inhibitory (7) or no effect (5) on the 20 neurones tested. In the presence of the 5-HT(7) antagonist SB 258719 the 5-CT excitation was attenuated. Furthermore, the excitatory response of NTS neurones evoked by electrical stimulation of the vagus nerve or activation of cardiopulmonary afferents with intra atrial phenylbiguanide was attenuated by SB 258719. The inhibitory action of 5-CT was unaffected by SB 258719 and the 5-HT(1A) antagonist WAY-100635. WAY-100635 failed to have any effect on 5-CT and vagal afferent-evoked excitations. CONCLUSIONS AND IMPLICATIONS: Vagal afferent-evoked excitation of NTS neurones can be blocked by SB 258719, a selective 5-HT(7) antagonist. This observation further supports the involvement of 5-HT neurotransmission in NTS afferent processing.
Authors: I T Forbes; S Dabbs; D M Duckworth; A J Jennings; F D King; P J Lovell; A M Brown; L Collin; J J Hagan; D N Middlemiss; G J Riley; D R Thomas; N Upton Journal: J Med Chem Date: 1998-02-26 Impact factor: 7.446
Authors: Svetlana Mastitskaya; Egor Turovsky; Nephtali Marina; Shefeeq M Theparambil; Anna Hadjihambi; Sergey Kasparov; Anja G Teschemacher; Andrew G Ramage; Alexander V Gourine; Patrick S Hosford Journal: J Neurosci Date: 2020-03-04 Impact factor: 6.167