Effects of serotonin on rat ileocolonic transit and fluid transfer in vivo: possible mechanisms of action.

Abstract

The aim was to investigate the action of serotonin (5HT) on function of the ileocolonic junction (ICJ) in vivo. In anaesthetised rats, models were developed to study the effects of intra-aortic (ia) serotonin on ileocolonic and colonic transit, and the effects on transit of a number of 5HT receptor antagonists. In the first series of experiments, a bolus of saline labelled with 99mTc DTPA was instilled 20 cm proximal to the ICJ and transit was assessed three hours later by the geometric centre of the spread of isotope. In the second series, similar techniques were used on the postcaecal colon and transit assessed two hours later. In the third series of experiments, the effects of ia 5HT on ileal net fluid flux was evaluated by standard perfusion experiments with 14C polyethylene glycol (PEG) 4000 as a non-absorbable marker in rat plasma-like electrolyte solution. Compared with ia saline, 5HT accelerated ICJ transit significantly (p<005). This acceleration was comparable with the effect of ia bethanechol. The effects of 5HT on ICJ transit were inhibited by the intraperitoneal (ip) infusion ofatropine, the 5HT receptor antagonists, methysergide, ketanserin, zacopride, and the 5HT4 agonist, SC53116. Methysergide, zacopride, and SC53116 given with ia 5HT slowed ICJ transit to rates below those of ia saline alone. When these same agents were given together with ia saline, the ICJ transit was not significantly altered. Serotonin, at the dose that accelerated ICJ transit, did not significantly alter colonic transit or ileal fluid transport. In conclusion, 5HT is a potent pharmacological stimulant oftransit across the rat ICJ in vivo; the action of 5HT is mediated partly through muscarinic neurones and several 5HT receptor subtypes.

Effects of tachykinins and 5‐hydroxytryptamine on intestinal secretion

“…However, the present results did not show that infusion of 5‐HT itself causes a significant reduction in absorption in comparison with the control group infused with saline instead of 5‐HT. This result is not surprising, because it has been established previously that exogenous 5‐HT is a more effective secreterogogue in the rat when administered luminally 13 than by close intra‐arterial infusion, 14 but it is not effective by intra‐aortic infusion 30 . The reason why intra‐aortic infusion was used in the present study was to obtain a clear comparison between the effects of the tachykinins and 5‐HT using an identical method.…”

Anti-mitogenic and apoptotic effects of 5-HT1B receptor antagonist on HT29 colorectal cancer cell line

“…Previous research has suggested that apoptosis is impaired in colon adenocarcinoma and one important goal in colorectal cancer is to Wnd some agents that increases the apoptosis process (Oosterbosch et al 1993). Our Wndings suggest that 5-HT 1A and 5-HT 1B receptors can be involved in pathophysiology of colorectal cancer and the role of 5-HT 1B receptor is of major importance.…”

“…Thus, an abnormality in the neuroendocrine system in the colon of patients with colon carcinoma might initiate or promote the development of the disease (El-Salhy et al 1998). Notwithstanding wide distribution of 5-HT 1 and 5-HT 2 group receptors in enteric nervous system and peripheral smooth muscle of alimentary tract (Oosterbosch et al 1993), there is a lack of evidence about the impact of 5-HT receptors in colon cancers. Having considered the role of 5-HT 1 receptors, especially 5-HT 1A,B,D subtypes in some malignancies, this study aims to investigate the role of 5-HT 1A,B,D receptor subtypes in colon cancer.…”

Validation of the measurement of low concentrations of 5-hydroxytryptamine in plasma using high performance liquid chromatography

“…The concentration of 5-HT in platelets, which is approximately equivalent to that of whole blood, is estimated to be ≤10 mol/l [4] and is consequently of the magnitude of 100 times greater than that found in platelet-depleted plasma (PDP), where any change is small and of short duration making detection and measurement difficult. 5-HT acts via a variety of receptors to modulate the motor, sensory and secretory functions of the gut [5][6][7]. Disorders of gastrointestinal sensorimotor function, such as irritable bowel syndrome (IBS) and functional dyspepsia (FD), have recently * Corresponding author.…”