1 The roles of acetylcholine (ACh) and tachykinins in neuro-neuronal transmission during ascending excitatory and descending inhibitory reflexes were studied by recording intracellular reflex responses of the circular muscle to physiological stimuli. Experiments were carried out in opened segments of guineapig ileum in an organ bath that was partitioned so that three regions could be independently exposed to drugs. 2 Ascending excitatory reflexes evoked by either distension from the serosal side or compression of the mucosa were depressed by 55% and 85%, respectively, in the presence of hexamethonium (200 gM) and by 30% and 45%, respectively, by a desensitizing concentration of the selective NK3 receptor agonist, senktide (1 gM), in the chamber in which reflexes were initiated. Together, hexamethonium and senktide abolished reponses to compression. A residual response to distension persisted. This was abolished by hyoscine (1 uM).3 Hexamethonium (200 gM) abolished ascending reflexes when applied to the region between the stimulus and the recording sites, or to the recording chamber. 4 Descending reflex responses were reduced by 35% by synaptic blockade in the stimulus chamber with physiological saline containing 0.1 mM Ca2" plus 10 mM Mg2'. Senktide (1 gM) in the stimulus chamber reduced distension reflexes to the same extent as synaptic blockade, whereas hexamethonium (200 gM) and hyoscine (1 gM) depressed responses by less than 20%. Responses to compression were reduced by 40% by senktide alone, while senktide and hexamethonium together reduced responses by 60%, an effect similar to synaptic blockade. Under these conditions, hyoscine in the stimulus chamber restored reflexes evoked by distension, but did not alter those evoked by mucosal compression. 5 Total synaptic blockade in the intermediate chamber, between stimulus and recording sites, reduced descending reflex responses by more than 90%. In contrast, hexamethonium (200 gM) had no effect and hyoscine (1 gM) reduced only the responses to distension (by 30%). Senktide (1 gM) depressed responses to both stimuli by approximately 80%.6 Application of hexamethonium (200 gM) to the recording chamber depressed descending reflex responses to distension applied in the near stimulation chamber by 15%, but had no effect on responses to compression in the near chamber or to either stimulus applied in the far chamber. 7 Descending reflexes evoked by near chamber stimuli were unaffected by hyoscine (1 gM) or senktide (1 gM) applied to the recording chamber; hyoscine enhanced reflexes evoked by compression in the far chamber by 50%. 8 For the ascending excitatory reflex pathway, it is concluded that transmission from sensory neurones is mediated by ACh acting via both nicotinic and muscarinic receptors, and by tachykinins acting at NK3 receptors. Transmission from ascending interneurones appears to be predominantly via nicotinic receptors. The descending inhibitory pathways are more complex, and while transmission from sensory neurones involves nicotinic, muscarinic ...

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1 The present study was undertaken to ascertain whether 5-hydroxytryptamine (5-HT) acting at either 5-HT3 or 5-HT4 receptors plays a significant role in motility reflexes in the guinea-pig small intestine. 2 An isolated segment of small intestine was opened along its mesenteric border and pinned, mucosa uppermost, in a three chambered organ bath so that the oral, middle and anal regions of a single preparation could be separately superfused. 3 Conventional intracellular recording methods were used to monitor the responses of the circular muscle in the oral or the anal end chambers when distension was applied in either of the other two chambers or the mucosal villi were compressed in the middle chamber. Drugs were added to the middle chamber.4 5-HT3 receptor antagonists (tropisetron, 0.1-101iM; granisetron, 1 11M and BRL46470, 1 gM) depressed the ascending excitatory reflex evoked by these stimuli but had no effect on the descending inhibitory reflex. The depression of the excitatory reflex was observed whether the reflex was evoked from the chamber containing the drug or was simply conducted, via interneurones, through this chamber. 5The 5-HT4 receptor antagonist, (1 PM), had no significant effect on either the ascending or descending reflex pathways. However, 5-HT4 receptors were present as cisapride (0.1 M) significantly enhanced the ascending excitation without affecting the descending inhibition. This effect of cisapride was converted to a significant depression of the ascending reflex by SDZ 205-557. 6 The results suggest that 5-HT3, but not 5-HT4, receptors play an important role in the ascending excitatory reflex and that these receptors may be on interneurones in the reflex pathway.

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