SENSITIVITY TO 5-HYDROXYTRYPTAMINE IN DIFFERENT AFFERENT SUBPOPULATIONS WITHIN MESENTERIC NERVES SUPPLYING THE RAT JEJUNUM

1. This study was performed to elucidate the type of afferents that me diate the multiple actions of 5-hydroxytryptamine (5-HT) on mesenteric nerve discharge. Electrophysiological recordings were made from mesen teric afferents innervating the mid-jejunum of the urethane-anaestheti zed rat. The discharge of single nerves within the whole nerve recordi ng was monitored using waveform discrimination software. 2. Afferents responded to 5-HT in one of two ways: a short latency, transient excit ation mediated big 5-HT3 receptors, or a delayed onset, more prolonged effect that was 5-HT2A receptor mediated. Afferents showing the 5-HT3 -mediated response did not respond to luminal distension but were sens itive to intraluminal hydrochloric acid (150 mM) in twenty-eight of tw enty-nine experiments. In eight experiments, the 5-HT3-mediated respon se was reversibly abolished by a 2 min exposure to intraluminal applic ation of local anaesthetic (2 % Xylocaine).3. Mechanosensitive afferen ts which responded to distension (< 10 cmH(2)O) did not show a 5-HT3-m ediated response (P = 0.92, n = 14), and maintained this mechanosensit ivity after luminal anaesthesia. Mechanosensitive afferents did show a secondary response to 5-HT that was significantly attenuated by atrop ine (100-200 mu g kg(-1)), whereas hexamethonium (8 mg kg(-1)) had no effect. 4. In animals whose vagal afferent contribution to their mesen teric nerves had been eliminated by chronic truncal vagotomy, the 5-HT 3-mediated response was absent in thirty-six of thirty-sh nerve bundle s. In contrast, mechanosensitivity to distension and the secondary res ponse to 5-HT could still be evoked. 5. These results suggest that 5-H T stimulates mesenteric afferents by a direct action on 5-MT3 receptor s that are present on vagal mucosal afferent terminals. The mucosal af ferent response to luminal acid, however, was unaffected by treatment with granisetron (0.5 mg kg(-1)) indicating that endogenous 5-HT from enterochromaffin cells is not essential for transduction of this lumin al signal. In contrast, mechanosensitivity in non-vagal afferents was modulated by 5-HT following an intestinal motor response which was inf luenced by cholinergic tone.