Overexpression of receptors for regulatory
peptides in various human diseases is reportedly of clinical interest. Among these
peptides,
bombesin and
gastrin-releasing peptide (GRP) have been shown to play a physiological and pathophysiological role in pancreatic tissues. Our aim has been to localize
bombesin receptors in the human diseased pancreas to identify potential clinical applications of
bombesin analogs in this tissue. The presence of
bombesin receptor subtypes has been evaluated in specimens of human pancreatic tissues with
chronic pancreatitis (n = 23) and ductal
pancreatic carcinoma (n = 29) with in vitro receptor autoradiography on tissue sections incubated with 125I-[Tyr4]-
bombesin or the universal
ligand 125I-[D-Tyr6, beta-Ala11, Phe13, Nle14]-
bombesin(6-14) as radioligands and displaced by subtype-selective
bombesin receptor agonists and antagonists. GRP receptors were identified in the pancreatic exocrine parenchyma in 17 of 20 cases with
chronic pancreatitis. No measurable
bombesin receptors were found in the
tumor tissue of ductal
pancreatic carcinomas, however, GRP receptors were detected in a subset of peritumoral small veins in 19 of 29 samples. Moreover, residual pancreatic islets in these tissues were shown to express the BB3 receptor subtype. These data demonstrate the presence of
bombesin receptors in three distinct tissue compartments of the pancreas, namely GRP receptors in the exocrine parenchyma in
chronic pancreatitis and in peritumoral vessels around ductal
pancreatic carcinomas, and BB3 receptors in residual pancreatic islets. Such a selective expression of
bombesin receptor subtypes in pancreatic tissues may not only be of pathophysiological significance but may represent the basis for potential diagnostic and therapeutic clinical applications of
bombesin analogs, including GRP receptor scintigraphy to differentiate
chronic pancreatitis from ductal
pancreatic carcinoma.