Physiology of isolated gastric endocrine cells

Abstract

The regulation of gastric acid secretion is achieved in the periphery by interplay between three major gastric endocrine cells: the enterochromaffin-like (ECL) cell, the gastrin or G cell, and the somatostatin or D cell. Regulation of these cells is via stimulatory or inhibitory paracrine, endocrine, and neural pathways. Upregulation of ECL function is determined by activation of CCK-B receptors, by gastrin, and by activation of beta-adrenergic receptors, as well as by acetylcholine in some (10-29%) of the cells. Gastrin and acetylcholine produce typical biphasic calcium signals. Inhibition of ECL cell histamine release and calcium signaling is produced by somatostatin acting at a type 2 receptor, histamine acting at a histamine-3 receptor, and by peptide PYY. Stimulation of ECL cells results in activation of chloride channels, and there is evidence that voltage-dependent calcium channels, along with the receptor-operated calcium channels, also are responsible for elevation of [Ca]i. Depolarization-activated K+ channels presumably restore the potential after depolarization by activation of the chloride channel. The D cell is activated by either gastrin or CCK and appears to be inhibited by acetylcholine and somatostatin. The G cell is activated by acetylcholine and gastrin-releasing peptide (GRP) and is inhibited by somatostatin. The functional integration of these three cell types is the primary determinant of the degree of stimulation of the parietal cell.