Regulation of Gastrointestinal and Colonic Transit by CCK Antagonists

CCK is an oligopeptide synthesized within the intestinal mucosa and released into the blood stream in response to the intake of a meal [1]. It is well-established that the main action of the hormone CCK is induction of gallbladder contraction [1] and stimulation of exocrine pancreatic secretion [2]. The recent elaboration of peptide hormone antagonists with CCK as a model has opened the way to conclusively investigate the physiological role of CCK. Thus, studies with loxiglumide, a specific and highly potent receptor antagonist of CCK, have recently shown that CCK is a physiologic mediator of the intestinal phase of meal-stimulated exocrine pancreatic enzyme secretion and gallbladder contraction in humans [3]. CCK binds, however, not only to receptors on smooth muscle cells of the gallbladder or pancreatic acini, but CCK binding receptors have also been found on smooth muscle cells of the stomach, small intestine, and colon [4]. Furthermore, it has been shown that CCK stimulates colonic myoelectric activity [5] and induces contraction of muscle strips from human taeniae coli [6]. Studies on humans have revealed that CCK directly inhibits gastric emptying [7] and radiologists have finally made use of CCK to accelerate the transit of a barium meal through the small intestine [8]. Thus, it is conceivable that CCK has a physiological role not only in stimulating pancreaticobiliary secretion, but it may be involved in the regulation of gastrointestinal motility as well.