Håkanson R, Tielemans Y, Chen D, Andersson K, Ryberg B, Mattsson H, Sundler F
Department of Pharmacology, University of Lund, Sweden.
Yale J Biol Med. 1992 Nov-Dec;65(6):761-74; discussion 827-9.
The enterochromaffin-like (ECL) cells represent the predominant endocrine cell population in the acid-producing part of the stomach of both experimental animals and man. These cells actively produce and store histamine in addition to an anticipated but as yet unidentified peptide hormone and are under the control of gastrin. An acute gastrin stimulus causes exocytosis of the cytoplasmic granules/vesicles (and release of histamine and activation of the histamine-forming enzyme, histidine 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 demonstrated following infusion of gastrin or following an increase in the concentration of circulating gastrin of endogenous origin. The growth of the ECL cells reflects an accelerated self-replication rate. As studied in the rat, the self-replication rate is accelerated quite soon after induction of hypergastrinemia (blockade of acid secretion), the rate is maximally elevated within two weeks and then declines to control values at ten and 20 weeks despite the sustained hypergastrinemia. Lifelong hypergastrinemia in rats is associated not only with ECL-cell hyperplasia 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 the ECL cells of histamine and that the histamine-depleted ECL cells respond to gastrin with hyperplasia in a manner identical to normal ECL cells. Other factors beside gastrin seem to participate in the control of ECL-cell function and proliferation. Although exogenous somatostatin is known to suppress the activity of the ECL cells, we have failed to obtain evidence that the somatostatin cells in the oxyntic mucosa play a role in the physiological control of the ECL cells. The vagus, however, is important for the ability of the ECL cells to respond to gastrin. This conclusion is based on the observation that vagal denervation suppresses the hyperplastic response of the ECL cells to gastrin. Porta-cava shunting, on the other hand, greatly enhances the responsiveness of the ECL cells to gastrin. The mechanism behind this effect is unknown.
肠嗜铬样（ECL）细胞是实验动物和人类胃产酸部位主要的内分泌细胞群。这些细胞除了能产生并储存一种预期但尚未明确的肽类激素外，还能主动产生和储存组胺，并且受胃泌素的调控。急性胃泌素刺激会导致细胞质颗粒/囊泡的胞吐作用（以及组胺释放和组胺形成酶——组氨酸脱羧酶的激活），而更持续的胃泌素刺激会使大鼠的ECL细胞先肥大，然后增生（细胞数量最多可增加五倍）。在输注胃泌素后或内源性循环胃泌素浓度升高后，这些效应均可得到证实。ECL细胞的生长反映了自我复制速率的加快。在大鼠身上的研究表明，高胃泌素血症（胃酸分泌受抑制）诱导后不久，自我复制速率就会加快，在两周内达到最高值，然后尽管高胃泌素血症持续存在，但在十周和二十周时又会降至对照值。大鼠终身高胃泌素血症不仅与ECL细胞增生有关，还与ECL细胞类癌的发生率增加有关。最近，我们发现，作为组氨酸脱羧酶自杀性抑制剂的α-氟甲基组氨酸能有效耗尽ECL细胞中的组胺，而组胺耗尽的ECL细胞对胃泌素的增生反应与正常ECL细胞相同。除胃泌素外，其他因素似乎也参与ECL细胞功能和增殖的调控。虽然已知外源性生长抑素会抑制ECL细胞的活性，但我们未能获得证据表明胃底黏膜中的生长抑素细胞在ECL细胞的生理调控中发挥作用。然而，迷走神经对于ECL细胞对胃泌素的反应能力很重要。这一结论基于以下观察结果：迷走神经切断术会抑制ECL细胞对胃泌素的增生反应。另一方面，门腔分流术会大大增强ECL细胞对胃泌素的反应性。这种效应背后的机制尚不清楚。
