Comparative inhibitory effects of pirenzepine and atropine on cholinergic stimulation of exocrine and endocrine rat 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.