The Role of CCK-A and CCK-B Receptors in the Trophic Control of Pancreas and Oxyntic Mucosa in the Rat
Sammanfattning: Cholecystokinin (CCK) and the related hormone gastrin have been claimed to exert trophic effects in the pancreas and gastrointestinal tract. Two types of receptors for CCK and gastrin are known to exist, the CCK-A and the CCK-B receptor. They differ in their affinty for CCK and gastrin. The CCK-A receptor has about 500 times higher affinity for sulfated than for non-sulfated CCK and gastrin, while the CCK-B receptor has about the same affinity for both sulfated and unsulfated CCK and gastrin. This work describes the role of CCK in maintaining a normal pancreatic weight in the rat and the close relationship between pancreatic growth on one hand and circulating concentration of CCK-8s and duration of exposure to CCK on the other. From the results we suggested that the trophic effect of CCK on the pancreas is mediated via direct stimulation of CCK-A receptors on the exocrine panceas and does not involve vagal pathways. It is also suggested that CCK can activatet the so-called ECL cells in the oxyntic mucosa by stimulating CCK-B receptors. The ECL cells are readily activated by gastrin and we conclude that CCK acts on the ECL cells in a gastrin-like manner. However, the ECL-cell-activating effect of CCK is physiologically relevant only under circumstances when circulating gastrin concentrations are low or when the sensitivity of the ECL cells is increased. Gastrin has been claimed to have a trophic effect on the whole digestive tract and pancreas. Our findings indicate that the trophic effect of gastrin is limited to the oxyntic mucosa. In support of this view we failed to demonstrate expression of mRNA for the CCK-B receptor in the intestines or pancreas of the rat. Portacaval shunting enhances the trophic action of CCK on the pancreas and of gastrin on the ECL cells. The results presented suggest that this is due to increased expression of CCK-A receptor mRNA in the pancreas and of CCK-B receptor mRNA in the oxyntic mucosa.
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