Modulation of rat pancreatic muscarinic cholinergic receptors by caerulein

To evaluate the modulation of pancreatic muscarinic receptors in two states of pancreatic growth, hypertrophy and hyperplasia, caerulein, a cholecystokinin analog, (1 microgram/kg) was administered thrice daily for 2 and 4 days to adult rats. After 2 days of treatment, pancreatic hypertrophy was well established as evidenced by increases in pancreatic weight, cellular mass and protein content. Using an increase in DNA content as an index of hyperplasia, we demonstrated that pancreatic hyperplasia occurred only after 4 days of caerulein treatment. Caerulein increased the concentration of muscarinic receptors per DNA in pancreatic homogenate by 57% over control value after 2 days of treatment without modification of the receptor affinity for the ligand QNB. This increase involved mainly receptors in the low affinity state for carbamylcholine and their concentration returned to control levels after 4 days of treatment. The functional capacity of the acini was significantly increased after 2 days of caerulein as amylase release (U/mg DNA) was significantly increased but the sensitivity of these acini to carbamylcholine was significantly decreased. After 4 days of caerulein, the functional capacity has returned towards control values but the sensitivity to carbamylcholine remained decreased. The increase in muscarinic receptor concentration could be ascribed to a general increase in cellular proteins, as part of the hypertrophic effect of caerulein. This specific effect would also explain the increased functional secretory capacity of the caerulein-treated acini but the decreased sensitivity to carbamylcholine probably resulted in changes at a postreceptor loci since the affinities of the muscarinic receptors for carbamylcholine remained unaffected.