Intracellular regulatory mechanisms of 5-HT release from enterochromaffin cells in intestinal mucosa

The gastrointestinal tract contains the largest amount of 5-hydroxytryptamine (5-HT: serotonin) in the body, approximately 95% of which is present in enterochromaffin (EC) cells in the mucosa. Numerous pharmacological studies using receptor agonists or antagonists have revealed that 5-HT release from EC cells is triggered or modulated via multiple autoreceptors and heteroreceptors present on EC cells. These include stimulatory receptors such as 5-HT3, muscarinic M-3, beta -adrenergic receptors, and inhibitory receptors such as 5-HT4, vasoactive intestinal polypeptide (VIP), tachykinin NK1, histamine H-3 receptors. 5-HT release from EC cells may occur via exocytosis that is dependent on intracellular Ca2+ concentration ([Ca2+](i)), as in many cell types. Recent digital imaging analysis of intracellular Ca2+ dynamics has also shown that muscarinic, alpha (2)-adrenergic and P2Y(1), receptor stimulation of EC cells increases [Ca2+](i) in EC cells in isolated mouse ileal crypts. However, the stimulus-secretion coupling and the cellular signalling pathways in EC cells seem to be much more complicated, and these results are somewhat controversial. These discrepancies could be explained by differences in experimental conditions such as the measurement of luminal or vascular release of 5-HT, and/or species differences. Molecular basis for the difference in these mechanisms still remains to be clarified.