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Gut peptide receptors in pancreata of azaserine-treated and normal control rats
1Department of Gastroenterology, University Hospital Leiden, The Netherlands.
Abstract:
Gut peptides are involved in the growth and carcinogenesis of the exocrine pancreas of rats after treatment with azaserine. However, little is known about the influence of azaserine on expression of gut peptide receptors in the pancreas of the rat. Cholecystokinin, bombesin, somatostatin, secretin, and vasoactive intestinal peptide receptors were therefore visualized and quantified by storage phosphor autoradiography in pancreata of either saline control or azaserine-treated rats. As expected, putative preneoplastic lesions were formed in the pancreata of the azaserine-treated but not in the control animals. The pancreata of control rats contained receptors for cholecystokinin, bombesin, somatostatin, secretin, and vasoactive intestinal peptide. Cholecystokinin receptors were of the A-type and showed, in contrast to the other receptors, a heterogeneous expression due to variability of the high-affinity receptors. In the pancreata of azaserine-treated animals a significantly increased binding capacity of high-affinity receptors fro cholecystokinin was found not only in atypical acinar cell nodules but also in non-nodular pancreas when compared to pancreas of control rats (P < 0.05). Neither atypical acinar cell nodules nor non-nodular pancreas of rats treated by azaserine were shown to possess receptors for the other four types of gut peptide receptors. The spectrum of peptide receptors in pancreas of control and azaserine-treated rats in this study may help to understand the mechanism whereby gut hormones may modulate pancreatic carcinogenesis.
Insights
Azaserine treatment in rats altered gut peptide receptor expression in the pancreas. Specifically, cholecystokinin receptor binding increased in preneoplastic lesions, suggesting a role in pancreatic carcinogenesis.
Area of Science:
- Gastroenterology
- Oncology
- Endocrinology
Background:
- Gut peptides influence pancreatic growth and carcinogenesis.
- Azaserine induces preneoplastic lesions in rat pancreas.
- Limited knowledge exists on azaserine's effect on pancreatic gut peptide receptors.
Purpose of the Study:
- To investigate the impact of azaserine on gut peptide receptor expression in rat pancreas.
- To quantify specific peptide receptors (cholecystokinin, bombesin, somatostatin, secretin, vasoactive intestinal peptide) in control and azaserine-treated rats.
Main Methods:
- Storage phosphor autoradiography was used to visualize and quantify peptide receptors.
- Pancreata from saline control and azaserine-treated rats were analyzed.
- Receptor binding capacity of high-affinity receptors was assessed.
Main Results:
- Control rat pancreas expressed receptors for cholecystokinin (A-type), bombesin, somatostatin, secretin, and vasoactive intestinal peptide.
- Azaserine-treated rats showed significantly increased high-affinity cholecystokinin receptor binding in atypical acinar cell nodules and non-nodular pancreas.
- No other tested gut peptide receptors were found in azaserine-treated rat pancreatic lesions.
Conclusions:
- Azaserine alters pancreatic gut peptide receptor expression, notably increasing cholecystokinin receptor binding.
- This altered receptor expression may play a role in the mechanisms of pancreatic carcinogenesis modulated by gut hormones.