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Modulation of peristalsis by 5-hydroxytryptamine in the mouse isolated colon 5-Hydroxytryptamine (5-HT) produces both facilitation (mediated by 5-HT3&4 receptors) and inhibition of peristalsis (mediated by 5-HT 7 receptors) in the guinea-pig ileum. (Tuladhar et al., 2003). In the present study we investigated the modulation of peristalsis by 5-HT in the mouse isolated colon and attempted to characterise the 5-HT receptors mediating the effect. Segments of proximal colon (3cm in length, next to the caecum) were obtained from BKW mice of either sex (38-42g), cannulated at the oral and anal ends and secured horizontally in a water-jacketed bath containing Krebs’ solution at 37ºC, gassed with 95% O2 and 5% CO2. Regular peristalsis was obtained with intraluminal pressures of 3-4 cm of water by the method described previously (Tuladhar et al., 2002). All drugs were added to the serosal side and agonists were added cumulatively at 6-8 minute intervals once regular peristalsis was obtained. The facilitation and inhibition of peristalsis was measured as the percentage decrease and increase from minimum and maximum interval between the peristaltic stokes respectively in the 5 min periods before the addition of 5-HT. Values shown are mean±s.e.mean with n indicating the number of animals. Statistical comparisons between the different treatments were made using Students t test, unpaired two tailed. Cumulative addition of 5-HT (0.001μM - 100μM) had no significant effect on peristalsis up to 0.1μM; it produced facilitation of peristalsis at 1 & 10μM (% decrease in interval at 1 & 10μM 45.4±18.4%, n=5 and 38.5±14.5%, respectively, n=5) and inhibition of peristalsis at 100μM (% increase in interval 320.5±101.1%, n=5). So, in all subsequent experiments 5-HT was tested at 1, 10 & 100μM. This paradigm greatly enhanced the facilitatory effect at 1 and 10μM of 5-HT (% decrease in interval 100±0%, n=6; i.e. a subsequent contraction started before the previous peristaltic contraction reached the anal end) but had no significant effect on peristalsis at 100μM. 5-Carboxamidotryptamine (n=6) and 5-methoxytryptamine (n=6) produced only facilitation of peristalsis at 1 & 10μM and produced no inhibitory effect at any concentration less than 100μM. In contrast, 8-0H-DPAT (10μM), α-methyl-5-HT (10μM), 2-methyl-5-HT (100μM), m-chlorophenylbiguanide (10μM) and 1-phenylbiguanide (100μM) produced only an inhibitory effect and abolished peristalsis in all tissues tested (n=6 all, the concentration at which peristalsis was abolished is shown in parenthesis). Addition of the 5-HT receptor antagonists (methysergide 1μM, ritanserin 0.1μM, ondansetron 1μM, GR113808 1μM, SB258585 1μM and SB269970 1μM; Hoyer et al., 2002) had no significant effect on their own and also failed to significantly alter either the facilitatory or inhibitory effects of 5-HT on peristalsis. The results indicate that 5-HT can produce both facilitation and inhibition of peristalsis in the mouse proximal colon. However, unlike in the guinea-pig ileum, the effects of 5-HT are unlikely to be mediated by either 5-HT3, 5-HT4 or 5-HT7 receptors. Further studies are required to elucidate the 5-HT receptors involved in the modulation of peristalsis in the mouse proximal colon
Hoyer, D et al. (2002). Pharmcol Biochem Behavior 71, 533-554. |
