THE YALE JOURNAL OF BIOLOGY AND MEDICINE 65 (1992), 431-436 Receptor Strategies in Pancreatitis

A variety of receptors on pancreatic acinar and duct cells regulate both pancreatic exocrine secretion and intracellular processes. These receptors are potential sites of action for therapeu-tic agents in the treatment of pancreatitis. Cholecystokinin (CCK) receptor antagonists, which may reduce the level of metabolic "stress " on acinar cells, have been shown to mitigate the severity of acute pancreatitis in a number of models. Not all studies have shown a benefit, however, and differences may exist between different structural classes of antagonists. Because increased pancreatic stimulation due to loss of feedback inhibition of CCK has been proposed to contribute to the pain of some patients with chronic pancreatitis, CCK receptor antagonists could also be of benefit in this setting. Somatostatin and its analogs diminish pancreatic secretion of water and electrolytes and have been effective in treating pancreatic fistulas and pseudocysts. These agents are also being evaluated for their ability to reduce pain in chronic pancreatitis (perhaps by reducing ductal pressure by diminishing secretory volume) and mitigating the severity of acute pancreatitis (possibly by reducing the metabolic load on acinar cells). Recently described secretin receptor antagonists may also have therapeutic value as a means of selectively inhibiting pancreatic secretion of water and electrolytes. Potent agonists and antagonists are becoming increasingly available for receptors involved in regulating the function of the gastrointestinal tract, including the exocrine pancreas. One of the first applications of such agents to clinical practice has been the use of secretin with or without cholecystokinin (CCK) or its analog caerulein in testing pancreatic exocrine secretory function [1]. More recently, the development ofCCK and secretin receptor antagonists and of octreotide, a clinically useful analog of somatostatin, has raised the prospect that therapies directed at modulating hormonal regulation of the pancreas may prove useful in treating acute or chronic pancreatitis