5-HT3 AND 5-HT4 RECEPTOR-MEDIATED FACILITATION OF THE EMPTYING PHASE OF THE PERISTALTIC REFLEX IN THE MARMOSET ISOLATED ILEUM

1 The patterns of intestinal motility and the effect of an increase in intraluminal pressure were studied in vitro on segments obtained from the marmoset small intestine. 2 Segments obtained from the distal hal f of the marmoset small intestine exhibited segmentation, consisting o f narrow annular contractions (lasting for 2-3 s) interposed between t he relaxed segments of varying length. The subsequent contractions occ urred slightly distal to the previous contraction, with ring-like cont ractions appearing to move in the aboral direction. Such segmentation was infrequent or absent in the segments obtained from the proximal ha lf of the small intestine. An increase in intraluminal pressure inhibi ted segmentation and finally produced peristalsis in most of the tissu es. 3 The influence of 5-hydroxytryptamine (5-HT) receptor agonists an d antagonists on the threshold of the peristaltic reflex was investiga ted in the segments obtained from the distal half of the intestine aft er segmentation had subsided. The effect of drug application to the se rosal surface was measured as a change in threshold pressure required to trigger the peristaltic reflex. A facilitation was defined in two w ays (a) as a reduction in the threshold pressure required to trigger t he reflex and (b) in those tissues that failed to respond with perista lsis on raising intraluminal pressure to the maximum attainable (1 kPa ), as a reduction in threshold pressure compared to this value. 4 5-HT (7.85+/-0.19), 5-methoxytryptamine (7.79+/-0.24), 5-carboxamidotrypta mine (6.66+/-0.13) and 2-methyl-5-HT (6.24+/-0.16) caused a concentrat ion related facilitation of the peristaltic reflex, the pD(2) values ( mean+/-s.e.mean) being shown in parentheses. 5 The concentration-respo nse curves to both 5-HT and 5-methoxytryptamine were dextrally shifted in a surmountable manner in the presence of GR 113808 (30 nM). pD(2) values for 5-HT and 5-methoxytryptamine were significantly decreased t o 6.98+/-0.24 and 6.83+/-0.36 respectively in the presence of GR 11380 8 (30 nM). 6 In the presence of a high concentration of (10 mu M) 5-me thoxytryptamine the subsequent addition of 2-methyl-5-HT (3-10 mu M) b ut not 5-methoxytryptamine (10 mu M) facilitated peristalsis; the effe ct of 3 mu M 2-methyl-5-HT was significantly decreased by 2 mu M ondan setron. 7 It is concluded that the facilitation of the peristaltic ref lex in the marmoset intestine induced by 5-HT at submicromolar concent rations involves a 5-HT4 receptor stimulation with an additional 5-HT3 receptor activation at higher concentrations.