Andersson K, Lindström E, Chen D, Monstein H J, Boketoft A, Håkanson R
Dept. of Pharmacology, University of Lund, Sweden.
Scand J Gastroenterol. 1996 Oct;31(10):959-65. doi: 10.3109/00365529609003114.
Gastrin activates histidine decarboxylase (HDC) and increases HDC and chromogranin A (CGA) mRNA levels in histamine-producing enterochromaffin-like (ECL) cells in the rat stomach. We have studied how histamine depletion by subcutaneous infusion of the HDC inhibitor alpha-fluoromethyl-histidine (alpha-FMH) affects how ECL cells respond to hypergastrinemia in terms of HDC and CGA mRNA levels.
In one experiment rats received alpha-FMH for 24 h. In another experiment rats received alpha-FMH, omeprazole (perorally), or a combination of the two drugs for 10 days. In a third experiment antrectomized rats were treated with alpha-FMH for 48 h. The circulating gastrin level, oxyntic mucosal histamine concentration, HDC activity, and HDC and CGA mRNA levels were determined.
alpha-FMH for 24 h increased the HDC and CGA mRNA levels without increasing the serum gastrin concentration. alpha-FMH for 10 days increased the serum gastrin concentration twofold. alpha-FMH + omeprazole resulted in the same serum gastrin concentration as after omeprazole alone (eightfold increase). HDC mRNA levels were higher after alpha-FMH + omeprazole than after omeprazole alone. alpha-FMH alone induced an HDC mRNA level that was similar in magnitude to that observed after omeprazole, although the serum gastrin concentration after alpha-FMH was much lower. In antrectomized rats alpha-FMH increased the HDC and CGA mRNA levels without increasing the serum gastrin concentration.
ECL-cell histamine depletion will increase mRNA levels for HDC and CGA by a gastrin-independent mechanism, possibly involving abolished histamine autofeedback inhibition.
胃泌素可激活组氨酸脱羧酶（HDC），并增加大鼠胃中产生组胺的肠嗜铬样（ECL）细胞中HDC和嗜铬粒蛋白A（CGA）的mRNA水平。我们研究了皮下注射HDC抑制剂α-氟甲基组氨酸（α-FMH）导致的组胺耗竭如何影响ECL细胞在HDC和CGA mRNA水平方面对高胃泌素血症的反应。
在一项实验中，大鼠接受α-FMH注射持续24小时。在另一项实验中，大鼠接受α-FMH、奥美拉唑（口服）或两种药物联合治疗10天。在第三项实验中，对切除胃窦的大鼠用α-FMH治疗48小时。测定循环胃泌素水平、胃黏膜组胺浓度、HDC活性以及HDC和CGA mRNA水平。
注射24小时的α-FMH可增加HDC和CGA mRNA水平，而不增加血清胃泌素浓度。注射10天的α-FMH可使血清胃泌素浓度增加两倍。α-FMH + 奥美拉唑导致的血清胃泌素浓度与单独使用奥美拉唑后相同（增加八倍）。α-FMH + 奥美拉唑组的HDC mRNA水平高于单独使用奥美拉唑组。单独使用α-FMH诱导的HDC mRNA水平与奥美拉唑治疗后观察到的水平相似，尽管α-FMH治疗后的血清胃泌素浓度要低得多。在切除胃窦的大鼠中，α-FMH增加了HDC和CGA mRNA水平，而不增加血清胃泌素浓度。
ECL细胞组胺耗竭将通过一种不依赖胃泌素的机制增加HDC和CGA的mRNA水平，可能涉及消除组胺自身反馈抑制。
