Mediation by 5-HT3 receptors of an excitatory effect of 5-HT on dorsal vagal preganglionic neurones in anaesthetized rats: an ionophoretic study.
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.
Wang
Y
Y
Department of Physiology, Royal Free Hospital Medical School, London.
Ramage
A G
AG
Jordan
D
D
D000768:Anesthesia, General; D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D017829:Granisetron / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007478:Iontophoresis; D008297:Male; D009046:Motor Neurons / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D000077526:Tropisetron; D014630:Vagus Nerve / Q000166:cytology* / Q000187:drug effects / Q000502:physiology
D001645:Biguanides; D017829:Granisetron; D007211:Indoles; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D000077526:Tropisetron; C008846:phenyl biguanide