Pancreatic Cells Have Cell Surface Receptors Stimulated by Acetylcholine, Cholecystokinin, and Secretin
When binding sites on the surfaces of pancreatic acinar, centroacinar, or duct cells are occupied, the cells are stimulated to secrete. Each type of cell appears to have receptors for ACh as well as for cholecystokinin (CCK) and secretin.
ACh, released from nerve endings near the cells, stimulates secretion, as do CCK and secretin arriving in the blood. CCK is the primary hormonal stimulus for acinar cells, whereas secretin is the primary hormonal stimulus for centroacinar and duct cells. It appears, however, that maximal stimulation of the cells occurs when all receptors are occupied. Thus, acinar cells secrete most actively in the presence of all three ligands: ACh, CCK, and secretin. In this manner, secretin is said to potentiate, or increase, the action of CCK on acinar cells, and CCK potentiates the action of secretin on centroacinar and duct cells.Nerve fibers ending in the vicinity of pancreatic acinar glands originate from cell bodies in the ENS, traveling outside the gut wall and into the pancreas. 'Γhese neurons are stimulated to release ACh by impulses arriving from other neurons of the ENS, or by parasympathetic fibers arriving through the vagus nerve. VagaI stimulation of pancreatic secretion may arise as the result of several stimuli. The sight and smell of food induce centrally integrated vagal responses, leading to pancreatic secretion. This is known as the cephalic phase of pancreatic secretion, which is analogous in concept to the cephalic phase of salivary and gastric secretion. Distention of the stomach causes a vagovagal reflex stimulating pancreatic secretion, called the gastric phase of pancreatic secretion. The effects of the cephalic and gastric phases of pancreatic secretion are to “ready” the intestine for the imminent arrival of food by prior stimulation of pancreatic secretions.
I he third phase, or intestinal phase, of pancreatic secretion is the most intense and involves endocrine as well as neuronal stimuli.
This phase commences as food material from the stomach enters the duodenum. This leads to distention of the duodenum» which appears to produce enteric nerve impulses, resulting in ACh stimulation of pancreatic secretory cells. This stimulation reinforces and enhances the vagally mediated neuronal stimulation of the cephalic and gastric phases. The endocrine portion of the intestinal phase of pancreatic secretion occurs in response to the chemical stimulation that results from the presence of gastric contents in the duodenum. Peptides in the duodenal lumen, arising from the digestion of food protein, stimulate CCK production from endocrine cells in the duodenum. Fats in gastric ingesta also stimulate CCK secretion, whereas the low pH of material entering the duodenum from the stomach stimulates the secretion of secretin.This stimulatory pattern is logical and results in a coordinated pattern of digestion. Proteins (peptides) and fats stimulate, through CCK, the secretion of protein-digesting and fat-digesting enzymes. These enzymes function best in an alkaline environment, and so the acid secretions of the stomach must be neutralized in order for these enzymes to be effective. Acid conditions in the duodenum stimulate pancreatic bicarbonate secretion through secretin, leading to alkalization of the ingesta. As food is digested and absorbed and acid is neutralized, the stimuli for pancreatic secretion are removed, and the amount of secretion diminishes to low, basal rates.