Mechanism of hypergastrinaemia after nephrectomy in the rat.

Abstract

Bilateral nephrectomy in the rat is followed by hypergastrinaemia and by activation of gastric histidine decarboxylase. The enzyme activity is thought to reflect the concentration of circulating gastrin. While there is general agreement that post-nephrectomy hypergastrinaemia is primarily the result of loss of renal elimination of gastrin, it remained to be determined whether gastrin secretion could be stimulated in the hypergastrinaemic state and whether it contributed to the hypergastrinaemia. Histamine, but not pentagastrin, is known to evoke gastric acid secretion in the nephrectomized rat, and histamine, but not pentagastrin, was found to lower the serum gastrin level and the gastric histidine decarboxylase activity, indicating that after nephrectomy gastrin was still secreted and that the secretion could be suppressed by increased acid output. The importance of gastrin secretion for post-nephrectomy hypergastrinaemia was assessed further by investigating the effect of nephrectomy on the serum gastrin concentration in rats previously subjected to operations that had either reduced (e.g. antrectomy) or raised (e.g. antrum exclusion) the serum gastrin concentration. Post-nephrectomy serum gastrin levels co-varied with the levels before nephrectomy. Thus, the capacity to secrete gastrin was not abolished by nephrectomy. Finally, nephrectomy greatly affected the linear correlation between the serum gastrin concentration and the gastric histidine decarboxylase activity in a manner suggesting the operation of a gastrin-independent factor capable of activating the enzyme.