Chen D, Zhao C M, Nylander A G, Håkanson R
Department of Pharmacology, University of Lund, Sölvegatan 10, S-223 62 LUND, Sweden.
Cell Tissue Res. 1996 Apr;284(1):55-63. doi: 10.1007/s004410050566.
Previously, we have investigated the effects of short-term (minutes to hours) and long-term (weeks to months) stimulation with gastrin on the histamine-producing enterochromaffin-like (ECL) cells in the oxyntic mucosa of rat stomach. The present study examines the response of the ECL cells of freely fed rats to sustained hypergastrinemia over a time span of a few hours to four weeks. Sustained hypergastrinemia was induced by the continuous subcutaneous infusion of human Leu15-gastrin-17. The histidine decarboxylase (HDC) activity and histamine concentration in the oxyntic mucosa were monitored throughout the study. ECL cell profiles in electron micrographs were analysed planimetrically. The HDC activity displayed a 4-fold increase within the first two days. Subsequently, it remained at a plateau. The histamine concentration increased 2- to 3-fold in response to gastrin. The rise in histamine was slower than the rise in HDC activity. At no time point was there a reduced concentration of histamine. The ECL cells increased in size after 4 days of hypergastrinemia, reaching a maximum cell profile area after 2 weeks and remaining enlarged for the duration of the study. The secretory vesicles were reduced in number after 1 day, returning gradually to the pre-stimulation value thereafter; their volume density remained reduced during the 6-day observation period. Vacuoles started to appear after 1 day of hypergastrinemia and their number and volume density increased, reaching a maximum after 4 days. The number and volume density of the microvesicles increased and plateaued after 2 days of hypergastrinemia. The number of granules per cell profile was unaffected but their volume density was greatly reduced after 4 days of hypergastrinemia (reflecting the ECL cell hypertrophy). The present findings establish the time course of activation of the ECL cells in response to sustained hypergastrinemia over a time span of a few hours to four weeks; a new "steady state" situation at a high level of activity has been established after about a week.
此前，我们已经研究了胃泌素短期（数分钟至数小时）和长期（数周数月）刺激对大鼠胃泌酸黏膜中产生组胺的肠嗜铬样（ECL）细胞的影响。本研究检测了自由进食大鼠的ECL细胞在数小时至四周的时间段内对持续性高胃泌素血症的反应。通过持续皮下输注人亮氨酸15 - 胃泌素-17诱导持续性高胃泌素血症。在整个研究过程中监测泌酸黏膜中的组氨酸脱羧酶（HDC）活性和组胺浓度。对电子显微镜照片中的ECL细胞形态进行平面测量分析。HDC活性在头两天内增加了4倍。随后，它保持在一个稳定水平。胃泌素刺激后，组胺浓度增加了2至3倍。组胺的升高比HDC活性的升高要慢。在任何时间点组胺浓度都没有降低。高胃泌素血症4天后ECL细胞体积增大，2周后达到最大细胞形态面积，并在研究期间持续增大。分泌囊泡在1天后数量减少，此后逐渐恢复到刺激前的值；在6天的观察期内其体积密度持续降低。高胃泌素血症1天后开始出现液泡，其数量和体积密度增加，4天后达到最大值。高胃泌素血症2天后微囊泡的数量和体积密度增加并趋于稳定。每个细胞形态中的颗粒数量未受影响，但高胃泌素血症4天后其体积密度大幅降低（反映了ECL细胞肥大）。本研究结果确定了ECL细胞在数小时至四周的时间段内对持续性高胃泌素血症的激活时间进程；大约一周后建立了一种新的高活性“稳态”情况。
