Mediation by 5‐HT₃ receptors of an excitatory effect of 5‐HT on dorsal vagal preganglionic neurones in anaesthetized rats: an ionophoretic study

Abstract

1 Extracellular recordings were made from 141 vagal preganglionic neurones in the dorsal vagal nucleus (DVN). The effects of ionophoretic administration of 5-hydroxytryptamine (5-HT), the 5-HT3 receptor agonist, phenylbiguanide (PBG) and the antagonists, granisetron and tropisetron on these vagal preganglionic neurones were studied in pentobarbitone sodium anaesthetized rats. 2 Ionophoretic application of 5-HT at low currents (< 10 nA) increased the activity in 46 (73%) of 63 neurones tested. Application of granisetron (5-20 nA) or tropisetron (5-20 nA) abolished or attenuated the 5-HT excitatory responses in 8 out of 11 and 5 out of 5 neurones respectively. At the currents used, neither antagonist had any effect on baseline firing rate. 3 Ionophoresis of the selective 5-HT3 receptor agonist, phenylbiguanide (0-40 nA) excited 54 (82%) of the 66 vagal neurones tested, whilst the remaining 12 neurones were unaffected. 4 Granisetron applied either ionophoretically (8/11) or intravenously (3/3), abolished or attenuated the excitations evoked by PBG. Similarly, tropisetron administered either ionophoretically (2/3) or intravenously (2/2), attenuated the PBG excitation. In contrast, the PBG excitations were unaffected by the 5-HT2 receptor antagonist, cinanserin (2/2), and the selective 5-HTlA receptor antagonist, WAY-100802 (6/6). 5 In conclusion, excitation of vagal preganglionic neurones evoked by ionophoretic application of 5-HT is mediated in part by 5-HT3 receptors and activation of 5-HT3 receptors on and/or in the vicinity of vagal motoneurones causes excitation of these neurones.

The effect of 5‐HT and selective 5‐HT receptor agonists and antagonists on rat dorsal vagal preganglionic neurones in vitro

“…This corresponds to recent evi-(c) At a higher dence suggesting a high level of 5-HT,A receptor mRNA prese to 5-HT was sent in the dorsal motor nucleus of the vagus of the rat % reduction was (Pompeiano et al, 1994;Wright et al, 1995) and also, to in vivo work where 5-HT increases spontaneous activity of antidromically identified DVMs via a 5-HT2A 2C receptor (Wang et al, 1995a Wang et al, 1995b). However, it has not been determined whether this effect is a direct, postsynaptic one, a presynaptic action or a combination of both effects as 20 mV observed within the NTS (Glaum et al, 1992).…”

“…Finally, all these studies were carried out on spontaneously firing neurones; therefore little is known about the subthreshold effects of 5-HT on DVMs. This is essential if the role of 5-HT in modulating DVMs is to be defined, as in vivo studies have shown that the majority of DVMs do not spontaneously fire action potentials (Wang et al, 1995b) whereas an in vitro study stated that most DVMs were spontaneously active (Travagli et al, 1991).…”

The Role of 5-HT3 and Other Excitatory Receptors in Central Cardiorespiratory Responses to Hypoxia: Implications for Sudden Infant Death Syndrome

“…In the nucleus tractus solitarii (NTS), activation of 5-HT3 receptors blocks the chemoreflex bradycardia and inhibits both baroreflex and Bezold –Jarisch reflex responses (24–27). In the dorsal vagal motor nucleus, another brainstem site that contains CVNs, activation of 5-HT3 receptors mediates excitation of CVNs (28, 29). Furthermore, 5-HT3 receptors are involved in physiological responses to hypoxia in the peripheral nerve system.…”

Modifications of plasma 5-HT concentrations during the allergic bronchoconstriction in guinea pigs

“…In the remaining experiments, guinea pigs sensitized to ovalbumin (OA) were submitted to an antigenic challenge with 400 μg/kg OA i.v., a dose that in this animal model usually produces an acute maximal bronchoconstriction in 2-6 min, with a gradual return to basal values in ∼15-30 min. To determine the functional role of 5-HT in the allergic bronchoconstriction, sensitized guinea pigs received a combination of 300 μg/kg methiothepin (antagonist of 5-HT 1 , 5-HT 2 , 5-HT 5 , 5-HT 6 , and 5-HT 7 receptors) [13,14] plus 3 mg/kg tropisetron (antagonist of 5-HT 3 and 5-HT 4 receptors) [15][16][17], both admin-istered by the i.v. route approximately 10 min before the antigenic challenge.…”