Involvement of Enteric Nervous System in the Regulation of Gastrointestinal Motility

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Serotonin (5-HT)-containing neurons in the gastrointestinal (GI) tract are thought to function as interneurons in the enteric nervous system. However, the details of the action of 5-HT on GI function has not been clarified. The purpose of the present study was to clarify the functional role of 5-HT on the motor activity of the intestine by using an ex vivo model of isolated, vasculary perfused rat duodenum. We especially saught to investigate the involvement of 5-HT3 and 5-HT4 receptors on peristaltic movement of the bowel.Method : The duodenal segment between pylorus and ligament of Treiz was vascularly perfused with O2 saturated Krebs' bicarbonate solution containing 3% dextran and 0.2% BSA.The motor activity was measured by a manometric method as follows : two manometric catheters were inserted through the pylorus and the tips were placed at 3 and 8 cm distant from the pylorus. Motor activity of duodenum in p-chlorophenylalanine (PCPA) treated animala, 5-HT depleted model, was exami … More ned in ex vivo isolated vascularly perfused preparation. Different 5HT receptor antagonists such as methysergide (5-HT1), ketanserin (5-HT2), granisetron and azasetron (5-HT3) and SB204070 (5-HT4) were introduced into the perfusate. The effect of these drugs on motor index (MI), %MI (% of control value) and frequency were compared with controls.Result : In normal conditions the motor activity was observed to consiste of a period of quiescence followed by contractions. Such contractile activity was defined as clusters of phasic contractions (COC). The frequency of CPC was 0.991+0.052/min, the duration was 30.0+2.0sec and the MI was 655+89cm H20/sec. Both mucosal and musclar layr 5-HT content were significantly lower than that in controls. Neither 5-HT1 (1 mM methysergide) nor 5-HT2 (10 mM ketanserin) changed the pattern of CPC.5-HT3 (0.1 nM granisetron) decreased % MI and the frequency of CPC.5-HT4 (0.1 nM SB204070) did not affect the frequency of CPC,however it decreased % MI of CPC.Conclusion : Endogenous 5-HT may affect the motor activity in the rat duodenum and this action seems to be mediated by 5-HT3 and 5-HT4 receptpors. Less