5‐HT3 and 5‐HT4 receptor‐mediated facilitation of the emptying phase of the peristaltic reflex in the marmoset isolated ileum

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Abstract
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 half of the marmoset small intestine exhibited segmentation, consisting of narrow annular contractions (lasting for 2–3 s) interposed between the relaxed segments of varying length. The subsequent contractions occurred slightly distal to the previous contraction, with ring-like contractions appearing to move in the aboral direction. Such segmentation was infrequent or absent in the segments obtained from the proximal half of the small intestine. An increase in intraluminal pressure inhibited segmentation and finally produced peristalsis in most of the tissues. 3 The influence of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists on the threshold of the peristaltic reflex was investigated in the segments obtained from the distal half of the intestine after segmentation had subsided. The effect of drug application to the serosal surface was measured as a change in threshold pressure required to trigger the peristaltic reflex. A facilitation was defined in two ways (a) as a reduction in the threshold pressure required to trigger the reflex and (b) in those tissues that failed to respond with peristalsis 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-carboxamidotryptamine (6.66±0.13) and 2-methyl-5-HT (6.24±0.16) caused a concentration related facilitation of the peristaltic reflex, the pD2 values (mean±s.e.mean) being shown in parentheses. 5 The concentration-response curves to both 5-HT and 5-methoxytryptamine were dextrally shifted in a surmountable manner in the presence of GR 113808 (30 nM). pD2 values for 5-HT and 5-methoxytryptamine were significantly decreased to 6.98±0.24 and 6.83±0.36 respectively in the presence of GR 113808 (30 nM). 6 In the presence of a high concentration of (10 μm) 5-methoxytryptamine the subsequent addition of 2-methyl-5-HT (3–10 μm) but not 5-methoxytryptamine (10 μm) facilitated peristalsis; the effect of 3 μm 2-methyl-5-HT was significantly decreased by 2 μm ondansetron. 7 It is concluded that the facilitation of the peristaltic reflex in the marmoset intestine induced by 5-HT at submicromolar concentrations involves a 5-HT4 receptor stimulation with an additional 5-HT3 receptor activation at higher concentrations.