Antagonism Of Receptors For Bombesin, Gastrin And Cholecystokinin In Pancreatic-Secretion And Growth

The effects of bombesin, gastrin and cholecystokinin (CCK) on amylase secretion from the isolated rat pancreatic acini and on DNA synthesis (as biochemical indicator of trophic action) in the pancreas have been examined in 48-hour fasted and 16-hour refed rats with and without administration of specific receptor antagonists for bombesin, gastrin and CCK. Studies on the isolated rat acini revealed that bombesin, gastrin and CCK-8 all showed the same efficacy in their ability to stimulate amylase release. RC-3095, bombesin pseudo-peptide antagonizing bombesin receptors, was effective only in suppressing the amylase response to bombesin but not to gastrin or CCK. Benzodiazepine receptor antagonists for gastrin (L-365,260) and for CCK (L-364,718) showed higher efficacy in the inhibition of amylase release induced by pentagastrin and CCK, respectively, but failed to affect that induced by bombesin. These peptides administered 3 times daily for 48 h in fasted rats increased the rate of DNA synthesis as measured by the incorporation of [H-3]thymidine into DNA. The blockade of bombesin receptors abolished the DNA synthesis induced only by bombesin but not by gastrin or CCK. The blockade of gastrin receptors by L-365,260 suppressed the DNA synthesis induced by gastrin while the antagonism of CCK receptors by L-364,718 was effective only against CCK. Refeeding of 48-hour fasting rats strongly enhanced DNA synthesis which was significantly reduced by blocking only the CCK receptors (with L-364,718), but not the bombesin (with RC-3095) or gastrin receptors (with L-365,260). This study indicates that the secretory stimulation of pancreatic acini and DNA synthesis can be achieved by exogenous bombesin, gastrin and CCK acting via separate receptors, but that only CCK plays the major role in the postprandial stimulation of the growth of pancreatic tissue.