GASTROESOPHAGEAL AFFERENT AND SEROTONERGIC INPUTS TO VAGAL EFFERENT NEURONS

Peripheral 5-HT3 receptor mechanisms are involved in activation of gas trointestinal (GI) mucosal vagal afferent fibres. 5-HT3 receptor mecha nisms in the central nervous system (CNS) may be involved in behaviour al and reflex motility responses. This study investigates the processi ng of different sensory inputs in the CNS and the involvement of 5-HT3 receptors at these different levels. In Urethane (1.5 g/kg, i.p.) ana esthetized, splanchnectomized ferrets, the jugular vein was cannulated for intravenous (i.v.) drug injection, and the coeliac axis for intra arterial (i.a.) injection close to the upper GI tract. The carotid art ery was intubated with a T-cannula for CNS-directed intracarotid (i.c. ) injections. An intragastric cannula was used for fluid distension (4 0-50 ml), and an oesophageal catheter for balloon distension (2 ml). E fferent fibres were dissected from the right cervical vagus for single -unit recording. Nineteen single vagal efferent fibres were selected, with low frequency resting discharge (2.5 +/- 0.3 impulses/s), but no respiratory or cardiovascular phasic input. All responded rapidly (< 2 .5 s) to gastric distension (532 +/- 230% change in firing rate) and o esophageal distension (300 +/- 170%). Gastric distension caused excita tion in 14 fibres, inhibition in 4 fibres, and a biphasic response in 1. Oesophageal distension excited 16 and inhibited 3. Discharge was al so influenced by i.a. injection of 5-HT or the 5-HT3 receptor agonist 2-methyl 5-HT (10-100 mu g) in all fibres tested. These responses cons isted of rapid (< 2.5 s) and powerful changes in firing rate, with exc itation, inhibition or biphasic responses. 65% of responses to i.c. or i.v. injection were opposite in direction to those after dose i.a. in jection, indicating the activation of a different population of recept ors. No differences were seen between effects of i.c. and i.v. injecti ons. The 5-HT3 receptor antagonist granisetron (100 mu g/kg, i.v.) blo cked or reduced efferent responses to 5-HT receptor agonists, whereas responses to gastric and oesophageal distension were unchanged. Thus t here is extensive convergence of inputs from gastric and oesophageal m echanoreceptors onto vagal motorneurones. These central effects of mec hanical stimuli do not involve 5-HT3 receptor mechanisms. Other 5-HT3 receptor inputs are evident, probably peripherally from GI mucosal aff erent fibres and from within the CNS.