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The acute and chronic effects of hydrocortisone on exocrine pancreatic function were examined in the isolated perfused rat pancreas. In the first part of this study, rats were given subcutaneous injections of hydrocortisone at doses of 1.25, 2.5, 5, and 10 mg/kg body wt once daily for 7 days. Trypsin and lipase secretion in response to 100 pM cholecystokinin-octapeptide was significantly increased in rats with the two highest doses of hydrocortisone compared with controls, irrespective of whether calculated as the total amount of stimulated output of enzymes or related to the secretion of enzyme to the pancreas content. On the other hand, the secretory responsiveness of amylase to 100 pM cholecystokinin-octapeptide was maximal at the 5-mg dose, and decreased with higher doses. In the second part, 100 μM hydrocortisone was superimposed for 20 min on 100 pM cholecystokinin-octapeptide stimulation to examine the acute effects of hydrocortisone on exocrine pancreatic function in the isolated perfused rat pancreas. Addition of hydrocortisone caused a significant inhibition of the secretion of pancreatic juice and amylase. The present study has clearly demonstrated the dual effects of glucocorticoids on the pancreas: inhibition and potentiation. There is a possibility that chronic treatment with large doses of glucocorticoid may sensitize the acinar cells and induce hypersecretion of trypsin and lipase, whereas acute treatment inhibits secretory function of exocrine pancreas.

The effects of pirenzepine on carbamylcholine-stimulated exocrine and endocrine pancreatic functions were compared with those of atropine in both the isolated pancreatic acini and the isolated perfused pancreas of rats. In the isolated acini pirenzepine and atropine produced a concentration-dependent inhibition of amylase secretion initiated by carbamylcholine. This inhibition resulted in a rightward shift in the dose-response curve for carbamylcholine-stimulated amylase secretion without altering the maximal increase in amylase secretion. Pirenzepine was, however, ~300 times less potent than atropine in inhibiting the stimulated amylase release. A similar difference in potency was observed with respect to carbamylcholine stimulation of pancreatic juice, amylase, and insulin release from the isolated perfused pancreas. The maximal inhibitory concentration of pirenzepine on a maximal effective concentration of carbamylcholine for stimulating pancreatic exocrine secretion was 10 μM, whereas that of atropine was 30 nM. The present data define the pirenzepine receptors in the exocrine and endocrine pancreas as low-affinity-type receptors.