Bombesin receptors in distinct tissue compartments of human pancreatic diseases

Overexpression of receptors for regulatory peptides in various human diseas es is reportedly of clinical interest. Among these peptides, bombesin and g astrin-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 cl inical applications of bombesin analogs in this tissue. The presence of bom besin 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 incubat ed with I-125-[Tyr]-bombesin or the universal ligand I-125-[D-Tyr(6), beta -Ala(11), Phe(13), Nle(14)]-bombesin(6-14) as radioligands and displaced by subtype-selective bombesin receptor agonists and antagonists. GRP receptor s were identified in the pancreatic exocrine parenchyma in 17 of 20 cases w ith chronic pancreatitis. No measurable bombesin receptors were found in th e tumor tissue of ductal pancreatic carcinomas, however, GRP receptors were detected in a subset of peritumoral small veins in 19 of 29 samples. Moreo ver, residual pancreatic islets in these tissues were shown to express the BB3 receptor subtype. These data demonstrate the presence of bombesin recep tors in three distinct tissue compartments of the pancreas, namely GRP rece ptors 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 subtyp es in pancreatic tissues may not only be of pathophysiological significance but may represent the basis for potential diagnostic and therapeutic clini cal applications of bombesin analogs, including GRP receptor scintigraphy t o differentiate chronic pancreatitis from ductal pancreatic carcinoma.