Depletion of Enterochromaffin-Like Cell Histamine Increases Histidine Decarboxylase and Chromogranin: A mRNA Levels in Rat Stomach by a Gastrin-Independent Mechanism

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Abstract
Background: 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 α-fluoromethyl-histidine (α-FMH) affects how ECL cells respond to hypergastrinemia in terms of HDC and CGA mRNA levels. Methods: In one experiment rats received α-FMH for 24 h. In another experiment rats received α-FMH, omeprazole (perorally), or a combination of the two drugs for 10 days. In a third experiment antrectomized rats were treated with α-FMH for 48 h. The circulating gastrin level, oxyntic mucosal histamine concentration, HDC activity, and HDC and CGA mRNA levels were determined. Results: α-FMH for 24 h increased the HDC and CGA mRNA levels without increasing the serum gastrin concentration. α-FMH for 10 days increased the serum gastrin concentration twofold. α-FMH + omeprazole resulted in the same serum gastrin concentration as after omeprazole alone (eightfold increase). HDC mRNA levels were higher after α-FMH + omeprazole than after omeprazole alone. α-FMH alone induced an HDC mRNA level that was similar in magnitude to that observed after omeprazole, although the serum gastrin concentration after α-FMH was much lower. In antrectomized rats α-FMH increased the HDC and CGA mRNA levels without increasing the serum gastrin concentration. Conclusion: ECL-cell histamine depletion will increase mRNA levels for HDC and CGA by a gastrin-independent mechanism, possibly involving abolished histamine autofeedback inhibition.