THE BIOLOGY AND PATHOBIOLOGY OF THE ECL CELLS

The enterochromaffin-like (ECL) cells represent the predominant endocr ine cell population in the acid-producing part of the stomach of both experimental animals and man. These cells actively produce and store h istamine in addition to an anticipated but as yet unidentified peptide hormone and are under the control of gastrin. An acute gastrin stimul us causes exocytosis of the cytoplasmic granules/vesicles (and release of histamine and activation of the histamine-forming enzyme, histidin e decarboxylase), while a more sustained gastrin stimulus causes first hypertrophy and then hyperplasia of the ECL cells in the rat (at most , a fivefold increase in the cell number). These effects can be demons trated following infusion of gastrin or following an increase in the c oncentration of circulating gastrin of endogenous origin. The growth o f the ECL cells reflects an accelerated self-replication rate. As stud ied in the rat, the self-replication rate is accelerated quite soon af ter induction of hypergastrinemia (blockade of acid secretion), the ra te is maximally elevated within two weeks and then declines to control values at ten and 20 weeks despite the sustained hypergastrinemia. Li felong hypergastrinemia in rats is associated not only with ECL-cell h yperplasia but also with an increased incidence of ECL-cell carcinoids . Recently, we could show that alpha-fluoromethylhistidine, which is a suicide inhibitor of histidine decarboxylase, effectively depletes th e ECL cells of histamine and that the histamine-depleted ECL cells res pond to gastrin with hyperplasia in a manner identical to normal ECL c ells. Other factors beside gastrin seem to participate in the control of ECL-cell function and proliferation. Although exogenous somatostati n is known to suppress the activity of the ECL cells, we have failed t o obtain evidence that the somatostatin cells in the oxyntic mucosa pl ay a role in the physiological control of the ECL cells. The vagus, ho wever, is important for the ability of the ECL cells to respond to gas trin. This conclusion is based on the observation that vagal denervati on suppresses the hyperplastic response of the ECL cells to gastrin. P orta-cava shunting, on the other hand, greatly enhances the responsive ness of the ECL cells to gastrin. The mechanism behind this effect is unknown.