Effects of portacaval shunt on the rat stomach

Abstract

In portacaval-shunted rats, basal but not pentagastrin-stimulated acid secretion was higher than in sham-operated controls. The basal serum gastrin concentration was unchanged and the postprandial serum gastrin concentration lowered following portacaval shunt. Thus, gastrin is not responsible for the elevated basal acid secretion. The present study provides evidence that there is no trophic effect on the oxyntic mucosa as a whole and that there is no change in parietal cell-associated gastrin receptors after portacaval shunting. Interestingly, however, endocrine cells in the oxyntic mucosa (the histamine-containing ECL cells) proliferated greatly and the pentagastrin- and cholecystokinin octapeptide-induced activation of the histamine-forming enzyme, histidine decarboxylase, in these cells was much greater than in control rats. Analysis of the dose-response curves for the enzyme-activating effect of pentagastrin and cholecystokinin-octapeptide indicated that the D50 values for these two stimulants were not altered by shunting but that the maximal enzyme activation was greatly elevated. The enhanced enzyme activation can be partly, but not fully, explained by the fact that the ECL cells were increased in number. The enhanced response following portacaval shunt probably reflects also an increased number of gastrin receptors per ECL cell. The effect of portacaval shunting on gastric ECL cells can perhaps be explained by impaired degradation in the liver of intestinal substance(s) exerting a highly specific trophic effect on the ECL cells or, alternatively, causing an enrichment of gastrin receptors on these cells, thereby making them more sensitive to the trophic effect of gastrin. The ECL cell hyperplasia is manifest about 4 weeks after the shunting. A modified procedure for portacaval shunting which left the gastroduodenal vein (otherwise ligated) drained to the liver produced the same trophic effect as conventional portacaval shunt, suggesting an intestinal rather than gastroduodenal origin of the agent(s) responsible for the trophic action.

Evidence for a Regulatory Role for Histamine in Gastric Enterochromaffin-Like Cell Proliferation Induced by Hypergastrinemia

“…Portacaval shunting induces gastric mucosal ECL cell hyperplasia which is, paradoxically, associated with a decrease in gas trin concentrations in both serum and antral mucosa, and in the thickness of fundic mucosa in rats [14][15][16], The effect of portacaval shunting on gastric ECL cells may be explained by impaired hepatic degradation of intestinal substances which exert a specific trophic effect on the ECL cells. Alternatively, this postulated modulator may modulate gastrin receptor on the ECL cells, thereby mak ing them more sensitive to the trophic effect of gastrin [14][15][16], Additionally, the clinical observation that there is a low' incidence of carcinoids in patients with achlor hydria due to atrophic gastritis or pernicious anemia with decades of exposure to extremely high levels of gastrin suggests that other factors may be required to induce these tumors [37], ECL cells appear to be renewed through self-replica tion rather than through differentiation from stem cells in the progenitor zone [12], The rate of self-replication of ECL cells is modulated by serum gastrin [10,11], In our study using chromogranin combined with anti-BrdU dou ble-label staining, dividing ECL cells were directly visual ized by light microscopy. Most dividing ECL cells were localized to the basal portion of the oxyntic glands, espe cially in areas of micronodular ECL cell carcinoid tumors.…”

“…10, 11, 13], Factors other than gastrin, however, are involved in the regulation of ECL cell proliferation. As an example, portocaval shunt in rodents induces ECL cell hyperplasia although both se rum and antral gastrin concentrations are decreased in such animals [14][15][16], Thus, alterations in serum gastrin alone may not be responsible for induction of gastric mucosal ECL cell mitogenesis.…”

Activation and Hyperplasia of Gastrin and Enterochromaffin-Like Cells in the Stomach

“…10, tables II, III). There is no increase in the serum gastrin level and no hypertrophy or hyperplasia of the oxyntic mucosa as a whole [31] . Thus, the trophic effect is on the ECL cells specifically.…”

Increased Expression of Cholecystokinin‐A Receptor mRNA in Pancreas and Cholecystokinin‐B Receptor mRNA in Oxyntic Mucosa after Porta‐caval Shunting in Rats

“…Porta-caval shunting which is associated with hypogastrinaemia and normal plasma CCK levels (see also Ekelund et al 1985;Axelson et al 1990;, induced an exaggerated response of the pancreas to CCK-A receptor activation and of the ECL cells of the stomach to CCK-B receptor activation (Ekelund et al 1985;Axelson et al 1990;). …”

“…The growth-promoting effects of CCK-A receptor activation on the pancreas and of CCK-B receptor activation o n the ECL cells are exaggerated by porta-caval shunting despite the fact that this is not associated with elevated levels of either CCK-8s or gastrin in the circulation . We have suggested therefore that porta-caval shunting produces an exaggerated response to CCK and gastrin (Ekelund et al 1985;Axelson et al 1990;. If this is correct we should expect increased CCK-A receptor gene expression in the pancreas and CCK-B receptor gene expression in the ECL cells, which in turn might result in increased numbers of CCK-A and CCK-B receptors.…”