This study was designed to compare, on a molar basis, the effect of chronic bombesin, gastrin-releasing peptide (GRP) and caerulein on pancreatic growth in the rat. These 3 peptides were administered s.c. 3 times daily for 4 days at the following concentrations: 0.036, 0.36, 3.6 and 7.2 nmol/kg of body weight. Bombesin and GRP induced pancreatic growth in a dose-dependent manner from 3.6 nmol/kg. This growth was characterized by an increase in pancreatic weight, its protein and RNA contents but not in DNA content suggesting cellular hypertrophy. Caerulein exerted a biphasic effect on pancreatic growth, inducing cellular hypertrophy at low doses since 0.36 nmol/kg and atrophy with the highest dose (7.2 nmol/kg). Bombesin and caerulein (until 3.6 nmol/kg) increased the pancreatic content in chymotrypsin more than in amylase. The 7.2 nmol/kg caerulein treatment depressed all enzyme activities while the same dose of GRP increased pancreatic lipase content. It is concluded that (1) bombesin and GRP are equipotent trophic factors for the pancreas; (2) caerulein is the most potent factor and exerts a biphasic effect on pancreatic growth; (3) pancreatic growth and synthesis and/or secretion of enzymes are not regulated through the same mechanism.

Bombesin administered subcutaneously to rats, three times daily for four days, induces pancreatic growth at a dose of 10 micrograms/kg. Growth was characterised by an increased pancreatic weight and content in protein and RNA, accompanied by cellular hypertrophy. Chronic bombesin also enhanced the pancreatic content in chymotrypsin and to a lesser degree its contents in amylase and lipase. The volume of the secretion and the output of enzymes in response to CCK under an infusion of secretin, however, remained unchanged although the functional capacity of individual cells to secret amylase and lipase was reduced. It is concluded that chronic bombesin exerts a trophic action on the rat pancreas but decreases the sensitivity of each cell to hormonal stimulation.

To study the effects of chronic bombesin on pancreatic growth and secretion, rats were injected subcutaneously, 3 times daily for 4 days with either saline or bombesin (10 micrograms/kg). Bombesin significantly increased the pancreatic weight and content in protein and RNA but not in DNA. The ratios of the three former parameters to DNA increased, suggesting cellular hypertrophy. The pancreatic content in enzymes was also elevated, especially for chymotrypsin and to a lesser degree for amylase. However, the volume of pancreatic secretion and the output of enzymes in response to CCK under a continuous infusion of secretin remained unchanged. The in vitro secretory response to caerulein and bombesin was reduced for amylase and lipase. It is concluded that chronic bombesin exerts a trophic action on the rat pancreas but decreases the sensitivity of each cell to hormonal stimulation.

This work investigates the pancreatico-trophic action of bombesin, a peptide stimulating pancreatic secretion in vivo and in vitro and examines whether this effect is altered by CCK or secretin. Rats were injected three times daily for 5 days either with saline, bombesin (1 or 10 micrograms/kg), CCK (20 I.D.U./kg), secretin (20 C.U./kg) or a combination of bombesin and CCK or secretin. Bombesin alone induced growth of the pancreas beginning with the dose of 10 micrograms/kg. This growth was characterized by an increase of pancreatic weight, its protein, RNA and enzyme content, but not of its DNA content. The ratios of the three former parameters to DNA increased, suggesting cellular hypertrophy. Cholecystokinin alone exhibited a similar trophic action on the pancreas as bombesin. Secretin alone had no effect on pancreatic size and composition. Cholecystokinin and secretin did not modify the pancreatico-trophic response of bombesin. These findings suggest that bombesin, administered for 5 days in the rat, induces pancreatic growth due to cellular hypertrophy. Cholecystokinin has the same effect. However the mode of action, at the cellular level, of bombesin appears to be different from that of cholecystokinin.

This work investigates the effect, on the rat pancreas, of a chronic administration of bombesin in function of the dose and duration of treatment and examines whether this effect may be mediated by the release of endogenous gastrin or cholecystokinin. Bombesin, administered three times daily for 5 or 15 days, induced a marked increase in pancreatic weight, its protein, RNA and enzyme contents with the dose of 10 micrograms/kg body weight; the ratios of pancreatic weight, protein and RNA contents to DNA contents increased significantly after a 5 day treatment, suggesting cellular hypertrophy. Pancreatic DNA content was markedly enhanced after a 15 day treatment, suggesting cellular hyperplasia. Antrectomy decreased plasma gastrin levels, but did not alter the pancreatico-trophic action of a 10 micrograms/kg bombesin treatment for 5 days. Proglumide, an inhibitor of cholecystokinin and gastrin in the pancreas, did not affect the growth of the pancreas induced by a 10 micrograms/kg bombesin treatment for 5 days. It is concluded that chronic bombesin induces, in the rat pancreas, cellular hypertrophy or hyperplasia depending on the duration of treatment. Pancreatic hypertrophy is not mediated by the release of endogenous gastrin or cholecystokinin.

The comparative effect of a 50% proximal or distal enterectomy on the exocrine pancreas and the remaining intestine has been studied in the rat one month after operation. Distal enterectomy induces (1) growth of the pancreas, characterized by a parallel increase in pancreatic weight, protein, DNA, RNA, amylase, lipase and chymotrypsin content, (2) preferential adaptation of the remaining ileum. Proximal enterectomy did not modify the pancreatic parameters studied but brings about an adaptation of the duodenum, the remaining jejunum and the ileum. It is concluded that pancreatic and intestinal adaptations differ after proximal and distal enterectomy.

Gastrin has been proposed as a trophic factor for the pancreas. Extensive small-bowel resection increased transiently plasma gastrin levels in the rat and produced pancreatic growth. This growth was characterized by an increased pancreatic weight, protein and DNA content, and the occurrence of mitotic figures in acinar cells. In order to determine if gastrin is implicated in pancreatic hyperplasia, we induced endogenous variations of gastrin 3 weeks before small-bowel resection or transection. Hypogastrinemia was produced by antrectomy and hypergastrinemia by vagotomy plus pyloroplasty. Pyloroplasty alone was without any effect. All gastric operations alone enhanced though not significantly the weight of the pancreas and its content in protein and DNA. When performed before intestinal resection, they did not modify the hyperplastic response of the pancreas to the resection. Our findings do not support the views that antral gastrin exerts a trophic action on the rat pancreas and that gastrin is implicated in postresectional hyperplasia of the gland.

Because gastrin is thought to be a trophic agent for the digestive tract, we studied the effects of endogenous variations of plasma gastrin on the small intestinal mucosa after a 90 p. 100 jejunoileal resection in the rat. Hypogastrinemia was induced by antrectomy while hypergastrinemia resulted from vagotomy. Pyloroplasty had no effect on gastrinemia. Small bowel resection increased mucosal weight, DNA and protein content; these changes were more obvious in the jejunum and ileum than in the duodenum. Gastric operations performed before the resection did not significantly modify these parameters except for the level of protein. Our results indicate that endogenous gastrin plays no role in the adaptive growth response of the intestinal mucosa after extensive small bowel resection.

Extensive small bowel resection produces pancreatic hyperplasia and increases plasma gastrin levels in the rat. Because gastrin is known as a trophic factor for the exocrine pancreas, we studied the effect of endogenous variations of gastrin induced by different gastric operations on the rat pancreas in both resected and transected animals. Vagotomy increased plasma gastrin level while antrectomy decreased it; pyloroplasty was without any effect. These gastric operations enhanced slightly but not significantly the pancreatic weight, its protein and DNA content. A 90% jejunoileal resection alone increased markedly these parameters while mitotic figures appeared in acinar cells. Pyloroplasty, vagotomy and antrectomy did not modify the changes induced by intestinal resection itself except the level of protein. These findings suggest that hypergastrinemia produced by intestinal resection is not responsible for pancreatic hyperplasia.