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 recording 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 (ICS 205-930) 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-HT1A 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.