Rats were given injections of caerulein, secretin, or a combination of these two peptides subcutaneously 3 times daily for 5, 10, or 15 days. Caerulein produced significant dose- and time-dependent increases in pancreatic weight and content of DNA, RNA, protein, amylase, and trypsinogen. Secretin produced significant increases in pancreatic weight and content of RNA and lipase after 15 days of treatment. After only 5 days of treatment with a combination of secretin plus caerulein, pancreatic weight and content of RNA and protein more than doubled, and trypsinogen content increased more than fivefold. Comparing the averages across the 5-, 10-, and 15-day values, increases in weight, protein, and trypsinogen with the combination of secretin plus caerulein were significantly greater than the sum of the effects of the peptides given singly. Using increase in DNA content as an index of hyperplasia and increases in the ratios of pancreatic weight, RNA content, and protein content to DNA content as indices of hypertrophy, we concluded that caerulein produced both hyperplasia and hypertrophy of rat pancreatic acinar cells. Secretin markedly augmented the hypertrophic action of caerulein but did not alter its hyperplastic action.
In six dogs with pancreatic fistulas, secretin (500 ng . kg-1 . h-1) was given to provide a flow of pancreatic juice of about 1 drop/s. Amylase concentration was measured in each drop before and after rapid intraduodenal injection of L-tryptophan, sodium oleate, and NaCl or after rapid intraportal injection of cholecystokinin (CCK). Latency of response (time between injection and a sustained increase in amylase output greater than the mean + 3 SD of prestimulation output) was 0.30 min to tryptophan and 0.33 min to oleate. These were significantly (P less than 0.01) less than the latency to intraportal CCK (0.53 min). Atropine and truncal vagotomy increased the latency to tryptophan and oleate 10-fold but had no effect on the latency to intraportal CCK. We conclude that, since the latency of amylase response to intraduodenal stimulants was shorter than to intraportal CCK, the initial response is probably not due to release of hormones. The finding that atropine and vagotomy increased latency of response to intraduodenal stimulants indicates that a vagovagal cholinergic reflex mediates the early pancreatic enzyme response to intestinal stimulants.
Pentagastrin (1.5 mg/kg), 20% pure natural cholecystokinin (CCK, 37.5 Ivy dog U/kg) or secretin (25 microgram/kg) was given in a depot carrier subcutaneously to rats 3 times daily for 15 days. The dose of CCK and secretin was submaximal for pancreatic secretion, whereas the dose of pentagastrin was supramaximal for gastric acid secretion. The pancreatic wet weight increased by 12% (P less than 0.01) in the rats treated with pentagastrin, 57% (P less than 0.001) in those treated with CCK, and 9% (P less than 0.01) in those treated with secretin. In CCK-treated rats, the maximal protein and bicarbonate outputs in response to cholecystokinin increased proportionately to the increase in pancreatic weight, but maximal bicarbonate and protein outputs in response to secretin were unaltered. The secretin-treated rats showed a lowered basal secretion of bicarbonate and a lowered sensitivity to secretin stimulation, but the maximal bicarbonate and protein outputs to secretin and CCK were unchanged. Treatment with pentagastrin produced no significant changes in pancreatic responses to secretin or CCK. We conclude that 1) the increase in pancreatic weight produced by repeated injections of cholecystokinin was accompanied by proportional increase in functional capacity as reflected by the increased maximal bicarbonate and protein outputs in response to cholecystokinin, and 2) repeated administration of secretin decreased the sensitivity of the pancreas to secretin without altering maximal bicarbonate response.
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