Regulation of 5-hydroxytryptamine (5HT) release from the enterochromaffin cell: physiological and pathophysiological roles

Abstract

Approximately 90% of peripheral 5HT is stored in the enterochromaffin cells (ECs) which are dispersed over the intestinal mucosa. They were first described and characterised by Heidenhain in 1870 and given the name of enterochromaffin cells by Vialli and Erspamer. In 1937 these authors first isolated an amine from these cells, which they called enteramine and which was later shown to be identical to serotonin, discovered earlier by Rapport. Although 5HT is considered to be the most important mediator released from ECs, it should be emphasized that other mediators are stored in ECs as well and may be co-released with 5HT. They include motilin, substance P and opioid peptides, pro-dynorphins in particular. ECs are distributed in the whole mammalian intestine [1], and while there are no marked differences in their distribution along the cephalo-caudal axis, they are more concentrated in the crypts than in the villi. ECs are part the APUD system and can be characterised as neuro-endocrine cells because of the presence of chromogranin in the granules and synaptophysin in small vesicles. Some specific enzymes, like neuro-specific enolase, are expressed as well. For example, the ECs express tryptophan-5-hydroxylase, the rate-limiting enzyme of 5HT synthesis. In a study using three-dimensional computer aided reconstruction of sections of the human stomach, the existence of cytoplasmic processes have been observed, similar to those expressed by ECs in primary culture. These processes contact neighbouring epithelial cells and neurones and might be of particular importance for the incorporation of the ECs in a complex regulatory structure. Another characteristic is the bipolar ultrastructure of these cells. Electron micrographs revealed that the majority of the granules are located